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1.
SAGE Open Med ; 11: 20503121231153755, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778198

RESUMO

Objective: The need for telemedicine was felt more than ever during the COVID-19 pandemic, which impacted health care worldwide. Therefore, this study aimed to determine the difficulties faced by patients in visiting the cardiac outpatient department during COVID-19, along with assessing the awareness and acceptability of telemedicine. Methods: In this cross-sectional study, selected patients presenting to outpatient department of a tertiary care cardiac hospital were interviewed regarding the difficulties faced by patients in visiting the outpatient department during COVID-19 and their awareness and acceptability of telemedicine using a self-designed structured questionnaire. Results: Of the 403 patients, 58.3% were male, the mean age was 53.04 ± 11.73 years, and most (77.7%) were urban residents. Ischemic heart disease was present in 69.5%, followed by hypertension (38.7%) and heart failure (29.3%). A total of 26.6% required emergency room visits. Limited appointments (55.6%) was the most common problem faced by patients during COVID-19, followed by financial issues (17.1%), fear of acquiring infection (13.4%), and limited mobility due to lockdown (22.6%). Only 12.2% were aware of telemedicine, 4.5% had previously used it, and 41.2% were willing to opt for telemedicine in the future. No internet access (39.2%) was the key barrier to the usage of telemedicine, followed by a lack of free medicine (39%) and a lack of a smart device (31.5%). Conclusion: Limited appointments due to COVID-19 restrictions has made it difficult for patients to visit the clinics, which has led to increased emergency room visits. Telemedicine awareness was found to be limited; however, many patients were willing to adopt it provided their limitations could be overcome.

2.
Lancet ; 398 Suppl 1: S2, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34227951

RESUMO

BACKGROUND: In 2017, the Ministry of Health in Gaza introduced Early Essential Newborn Care (EENC) as its primary maternal and neonatal care strategy. EENC comprises a package of simple evidence-based interventions that are delivered during labour and delivery, and in the early post-partum period, to prevent or treat the most important causes of morbidity and mortality in newborn babies. Four public maternity hospitals in Gaza, responsible for approximately 75% of all deliveries, began implementation of EENC in June, 2017. Clinical coaching was delivered by national facilitators over 2 days, and targeted all clinical staff in maternity and neonatal units. Subsequently, EENC quality improvement teams were formed to address contextual factors that influence practice. This study aimed to determine whether introduction of EENC resulted in changes in clinical practices for vaginal births. METHODS: A pre-intervention and post-intervention design was used to review key clinical practices before and after EENC introduction in the four hospitals. Trained data collection staff visited each hospital for 1 day in each of the months of March and June, 2017 (before EENC implementation), January and April, 2018 (in the early stages of EENC implementation), September, 2018, and June, 2019 (after full EENC implementation). Standard WHO data collection methods and tools were used to gather practice data using exit interviews and chart reviews of 10-15 randomly selected post-partum mothers who had delivered vaginally in the previous 2-24 h and had not experienced a newborn death or stillbirth. Delivery observations were conducted for five to ten randomly selected vaginal deliveries using a standard clinical skills observation checklist, beginning at the second stage of labour. The Ministry of Health in Gaza approved EENC assessments for programme use, and informed verbal consent was obtained before maternal interviews. No personal identifiers were used in assessments. FINDINGS: 259 maternal post-partum interviews and 139 observations of birth practices were done across the four maternity hospitals, representing 8·8% (259 of 2940) and 4·7% (139) of expected vaginal births during the observation periods, respectively. Comparing practices at baseline, early implementation, and after full implementation, significant trend improvements were noted for proportion of babies receiving thorough drying (0% [0 of 12], 49% [32 of 66], 72% [43 of 60], respectively, p<0·0004), immediate skin-to-skin contact (SSC) for less than 1 min (0% [0 of 14], 33% [43 of 127], 66% [72 of 110], p<0·0001), uninterrupted SSC for at least 60 min (0% [0 of 14], 21% [27 of 129], 48% [53 of 111], p<0·0001), uninterrupted SSC for at least 90 min (0% [0 of 14], 10% [13 of 129], 36% [39 of 110], p<0·0001), early breastfeeding (15-90 min after birth) (0% [0 of 15], 39% [50 of 130], 61% [65 of 107], p<0·0001), breastfeeding before separation (0% [0 of 15], 28% [36 of 131], 52% [56 of 108], p<0·0001), and exclusive breastfeeding before discharge (33% [5 of 15], 68% [89 of 131], 81% [87 of 107], p=0·0010). Average clinical practice scores rose from five of 42 (12%) to 16 of 42 (38%) and 24 of 42 (57%). Practice improvements were supported by updated clinical guidelines, hospital policies, and routines, by reorganisation of work, and by the provision of simple supplies, including gowns for mothers and caps for newborn babies. INTERPRETATION: The EENC clinical coaching approach coupled with regular self-assessments and action by hospital teams has significantly improved care practices during delivery and in the early post-partum period. It is possible that periodic cross-sectional practice reviews were not representative of routine practices, which may have varied with time of day, case load, and case complexity. Limitations were mitigated by assessing a systematic random sample of post-partum women delivering throughout the previous 24 h, and by measuring practices in two different time periods in each phase of implementation. Post-partum interviews were used to limit the Hawthorne effect. No other maternal or newborn initiatives were introduced during the study period, and no additional staff training was available, therefore the EENC approach was the primary influence on health worker practices. FUNDING: Support for this work was provided by WHO, occupied Palestinian territory.

3.
J Pak Med Assoc ; 71(5): 1428-1431, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34091628

RESUMO

OBJECTIVE: To determine the role of video-assisted thoracoscopy for evacuating retained / clotted haemothoraces to minimise the duration of chest tube drainage and length of hospital stay. METHODS: The prospective cohort study was conducted from July 2019 to February 2020 at the Department of Thoracic Surgery, Jinnah Postgraduate Medical Centre, Karachi, and comprised consecutive patients who underwent video-assisted thoracoscopy for retained or clotted haemothoraces. Outcome was measured as evacuation of retained haemothoraces resulting in partial or complete lung expansion and length of hospital stay. Data was analysed using SPSS 22. RESULTS: Of the 160 patients, 128(80%) were males and 32(20%) were females. The overall mean age was 36.08±11.91 years. Overall, 103(64.37%) patients underwent the procedure in within 4-7 days, and 57(35.63%) within 8-14 days. Complete lung expansion was achieved in 95(71.9%) patients when the procedure was performed in the first week, and in 37(28.1%) when performed in the second week (p=0.01). Within the first week, 87(84.4%) patients had shorter duration of stay compared to patients having undergone the procedure in the second week (p=0.001). Relapse of collection was found in 21(13.7%) patients. CONCLUSIONS: Video-assisted thoracoscopy was found to be a safe, reliable and effective technique for the evacuation of retained haemothorax in haemodynamically stable patients. Early intervention resulted in better outcome.


Assuntos
Hemotórax , Toracoscopia , Adulto , Feminino , Hemotórax/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Toracotomia , Resultado do Tratamento , Adulto Jovem
4.
Cureus ; 12(8): e9662, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32802623

RESUMO

Introduction Foreign body (FB) aspiration is a potentially lethal emergency and is not uncommon in adults. Rigid bronchoscopy (RB) is a useful procedure for the extraction of these FBs, and it has a high success rate. The aim of this study was to document the clinical presentation of FB aspirations and management outcomes of non-vegetative FB extraction using RB as a therapeutic modality. Method This prospective interventional study was conducted in the Department of Thoracic Surgery, Jinnah Postgraduate Medical Centre (JPMC), Karachi from May 2019 to April 2020. Patients of both genders of ages 12 years or above, presenting with FB aspiration were included. RB was performed in all patients. Results Chest radiograph (CXR) identified FBs in all 60 patients, 51 of whom were females and nine males. In 24 (40%) patients, a CT scan was performed to accurately localize the FB. Left bronchus was the most common location of the FB (n=39; 65%). Scarf pin was the most common type (n=45; 75%) of FB, followed by sewing needle (n=7; 11.7%), safety pin (n=5; 8.3%), and tire repair needle (n=3; 5%). In 53 (88.3%) patients, RB was successful in retrieving the FB. Thoracotomy was performed in the remaining seven patients due to inaccessibility. One (1.7%) patient died due to the rupture of the thoracic aortic aneurysm. Conclusion Accidental aspiration of pins and needles can be fatal in adults. RB is a life-saving modality for safely removing these FBs. However, thoracotomy should be used as a life-saving procedure in cases of FBs affecting secondary bronchi or beyond.

5.
Cureus ; 12(8): e9974, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32850270

RESUMO

Introduction In the elderly population, trauma is a leading cause of utilization of healthcare, institutionalization, disability, and mortality. In this study, we will assess the injury patterns and the factors associated with the outcomes of blunt thoracic trauma in elderly individuals. Methods This prospective observational study was conducted in the Department of Thoracic Surgery, Jinnah Postgraduate Medical Center, Karachi, Pakistan, from September 2019 to April 2020. The study included patients of both genders aged 60 years and above with blunt thoracic trauma. Patients with concomitant neurological injuries and penetrating trauma to the chest were excluded. Results There were a total of 80 patients in this study; majority were males (n = 66 [82.5%]). The mean age was 70.18 ± 8.3 years. Road traffic accident was the most common mode of injury (n = 45 [56.3%]) followed by fall (n = 32 [40%]). Hemothorax and hemopneumothorax were the most common primary diagnosis. Rib fractures were encountered in 72 (90%) patients. Mortality rate was 21.3% (n = 17). Factors significantly related to mortality were age ≥ 80 years (p = 0.00), tension pneumothorax (p = 0.036), pre-existing cardiopulmonary disease (p = 0.032), blood loss ≥ 500 mL (p = 0.004), flail chest (p = 0.018), and chest trauma score ≥ 5 (p = 0.001). Mean hospital stay in our study was 5.3 ± 3.4 days. Factors lengthening hospital stay by more than five days included lung contusion (p = 0.02), more than two rib fractures (p = 0.004), hemopneumothorax (p = 0.026), pneumonia (p = 0.003), acute respiratory distress syndrome (p = 0.003), and flail chest (p = 0.013). Conclusions Elderly patients with blunt thoracic trauma have higher mortality. Proactive evaluation of injuries using the chest trauma score in the elderly population helps in recognizing patients at high risk of mortality and helps in the timely management to prevent adverse outcomes.

6.
Cureus ; 12(12): e12404, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33532162

RESUMO

OBJECTIVE: To determine the early functional outcome of pulmonary decortication (PD) in patients having organized empyema thoracic (ET).  Methodology: This is a prospective study conducted at the Department of Thoracic Surgery, Jinnah Postgraduate Medical Center, Karachi from July 2019 to June 2020. The study included 76 patients referred to the department for assessment and surgery for the indication of organized empyema thoracis. After careful assessment and evaluation of the patients' computed tomography (CT) scans and pulmonary function tests (PFTs) in addition to their symptoms, history, etiology of empyema, physical examination and nutrition status, they were recommended pulmonary decortication to release the underlying entrapped lung. Functional improvement was measured in terms of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) three to six months after PD. RESULTS: A total of 76 empyema thoracis patients were included in the study. The mean age of participants was 33.4±11.9 years. The mean duration of empyema symptoms was 7.21±3.7 months. Majority were males (n=61; 80.3%). The full-lung expansion was achieved in 43 patients and partial lung expansion was achieved in 27 patients. The lung failed to expand in five patients. There was one death (lung failed to expand) due to respiratory failure as a result of septicemia. Most of the patients who achieved full-lung expansion had tuberculosis (26; 60.5%), followed by penetrating lung injury (7; 16.2%) and ruptured pulmonary hydatid cysts (5; 11.6%). Statistically significant association was found between etiology and full-lung expansion (p=0.042). Early functional improvement was seen in all patients with PD as mean FEV1 improved from 1.23±0.27 to 2.02±0.5 (63% increase; p<0.001) and FVC from 2.10±0.27 to 2.72±0.41 (29.7% increase; p<0.001). CONCLUSION: Based on the results obtained in the present study, it is concluded that pulmonary decortication in carefully selected patients has a vital role in significantly improving early functional results in terms of pulmonary functions.

7.
Molecules ; 21(11)2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27879669

RESUMO

In this study, we synthesised a morpholino nucleoside-uridine (MNA-U) phosphoramidite and evaluated the potential of a MNA-modified antisense oligonucleotide (AO) sequences to induce exon 23 skipping in mdx mouse myotubes in vitro towards extending the applicability of morpholino chemistry with other nucleotide monomers. We designed, synthesised, and compared exon skipping efficiencies of 20 mer MNA-modified 2'-O-methyl RNA mixmer AO on a phosphorothioate backbone (MNA/2'-OMePS) to the corresponding fully modified 2'-O-methyl RNA AO (2'-OMePS) as a control. Our results showed that the MNA/2'-OMePS efficiently induced exon 23 skipping. As expected, the 2'-OMePS AO control yielded efficient exon 23 skipping. Under the applied conditions, both the AOs showed minor products corresponding to exon 22/23 dual exon skipping in low yield. As these are very preliminary data, more detailed studies are necessary; however, based on the preliminary results, MNA nucleotides might be useful in constructing antisense oligonucleotides.


Assuntos
Distrofina/genética , Morfolinos/química , Mioblastos/efeitos dos fármacos , Compostos Organofosforados/síntese química , Uridina/análogos & derivados , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Éxons , Camundongos , Estrutura Molecular , Morfolinos/síntese química , Morfolinos/farmacologia , Mioblastos/citologia , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Uridina/síntese química , Uridina/química , Uridina/farmacologia
8.
Am J Case Rep ; 15: 291-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25031783

RESUMO

PATIENT: Male, 27. FINAL DIAGNOSIS: Recurrent epistaxis. SYMPTOMS: Nasal bleeding. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: Pediatrics and Neonatology. OBJECTIVE: Congenital defects/diseases. BACKGROUND: Recurrent epistaxis is a common disorder among children and young adults. We report an unusual cause, intranasal supernumerary tooth causing friction with Little's area of the nasal septum. CASE REPORT: A 22-year-old male presented with recurrent, mild, unilateral left-sided epistaxis once to twice per month for 3 years. This usually occurred after minor nasal trauma or rubbing his nose. The patient also suffered from recurrent tonsillitis. There was neither history of blood transfusion or nasal packing, nor a history suggestive of bleeding diathesis. Anterior rhinoscopy revealed ivory white nasal mass antero-inferiorly in the left nasal cavity touching Little's area. There was no bleeding. Nasal endoscopy showed a white cylindrical bony mass 1 cm long arising from the floor of the nose, with no attachment to the nasal septum or the lateral wall of the nose. Examination of the right nasal cavity was unremarkable. CONCLUSIONS: Nasal teeth result from the ectopic eruption of supernumerary teeth and may cause a variety of symptoms including recurrent epistaxis. Their clinical and radiologic presentation is so characteristic that their diagnosis is not difficult. CT scan is helpful in planning management. Early extraction prevents further complications and prevents further attacks of epistaxis.


Assuntos
Epistaxe/etiologia , Dente Supranumerário/complicações , Diagnóstico Diferencial , Endoscopia , Epistaxe/diagnóstico , Humanos , Masculino , Tomografia Computadorizada por Raios X , Extração Dentária/métodos , Dente Supranumerário/diagnóstico , Dente Supranumerário/cirurgia , Adulto Jovem
9.
J Org Chem ; 77(21): 9562-73, 2012 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-23039223

RESUMO

Synthesis of three pyrene-modified nucleosides was accomplished using the CuAAC reaction. Hereby, pyrene is attached either to the 5'-position of thymidine or to the 2'-position of 2'-deoxyuridine through triazolemethylene linkers, or to the 2'-position of 2'-deoxyuridine through a more rigid triazole linker. The three nucleosides were incorporated into oligonucleotides, and these were combined in different duplexes and other secondary structures, which were analyzed by thermal stability and fluorescence studies. The three monomers were found to have different impacts on the nucleic acid complexes. Hence, pyrene attached to the 5'-position shows a tendency for intercalation into the duplex as indicated by a general decrease in fluorescence intensity followed by an increase in duplex thermal stability. Pyrene attached to the 2'-position through a rigid triazole linker also shows a tendency for intercalation but with decrease in duplex stability, whereas the pyrene attached to the 2'-position through a triazolemethylene linker is primarily situated in the minor groove as indicated by an increase in fluorescence but here in most cases leading to increase in duplex stability. All three pyrene nucleotides lead to thermal stabilization of bulged duplexes and three-way junctions. In some cases when two pyrenes were introduced into the core of these complexes, the formation or disappearance of a fluorescence excimer band can be used to indicate the hybridization process. Hereby these oligonucleotides can act as specific recognition probes.


Assuntos
Nucleosídeos/síntese química , Nucleotídeos/síntese química , Oligonucleotídeos/química , Oligonucleotídeos/síntese química , Pirenos/química , Pirenos/síntese química , Pareamento de Bases , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Nucleosídeos/química , Nucleotídeos/química
10.
Org Biomol Chem ; 9(5): 1381-8, 2011 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-21210043

RESUMO

Four double-headed nucleosides were prepared by the CuAAC reaction. Hereby, a triazole-containing linker connects an additional thymine or adenine to the 2'-position of 2'-deoxyuridine, a thymine to the 5'-position of thymidine and a thymine to the 6'-position of an LNA-thymidine monomer. Whereas no conclusive recognition effects of the additional thymines were found when introduced in LNA or at the 5'-position, both thymine and adenine in the 2'-position were found to stabilise three-way junctions in both dsDNA and DNA : RNA contexts and to give cross-strand interactions in a DNA-duplex, when specifically introduced in a so-called (+1)-zipper motif.


Assuntos
Conformação de Ácido Nucleico , Ácidos Nucleicos/química , Nucleosídeos/síntese química
11.
Chemistry ; 16(43): 12904-19, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20886473

RESUMO

A series of six double-functionalised nucleosides, in which aromatic moieties were inserted into the 5'-(S)-C-position, were synthesised and incorporated into DNA duplexes. The aromatic moieties were thymine-1-yl, phenyl, 1,2,3-triazol-1-yl, 1,2,3-triazol-4-yl, 4-(uracil-5-yl)-1,2,3-triazol-1-yl and 4-phenyl-1,2,3-triazol-1-yl. The DNA duplexes were studied with UV melting curves, CD spectroscopy and molecular modelling. The results showed that the aromatic moieties in some cases interact in the minor groove forming DNA zipper structures. The strongest specific interaction was found between two thymines or between a thymine and a phenyl group in a crossed (-3)-zipper motif (i.e., with two base pairs interspacing the modifications). Modelling revealed that the interaction is aromatic stacking across the minor groove. Also, the extended uracil-triazole moiety demonstrated zipper contacts in the minor groove as well as binding to the floor of the groove.


Assuntos
DNA/química , Modelos Moleculares , Nucleosídeos/síntese química , Química Click , Nanotecnologia , Conformação de Ácido Nucleico , Nucleosídeos/química , Homologia de Sequência do Ácido Nucleico
12.
Rhinology ; 47(2): 214-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19593981

RESUMO

We report an unusual case of an accidental firearm injury, in a 35-year-old male firearm trainer, by a bullet cover fired in a retrograde manner, which was lodged in his right nasal cavity just reaching sphenoid sinuses without any neurological impairment. The extent of tissue damage and posterior extent of tract was assessed by plain radiography and CT scans. The bullet cover was recovered under endoscopic guidance and the wound sutured with a small defect left for healing by secondary intention keeping in mind second stage reconstruction of the persisting defect. On follow up the wound had healed with good esthetic results. The case showed that gunshot injuries can be treated primarily as well that undermining of the edges of wound and regular well-lubricated dressings are key to good healing.


Assuntos
Corpos Estranhos/cirurgia , Traumatismos Maxilofaciais/cirurgia , Nariz/lesões , Ferimentos por Arma de Fogo/cirurgia , Adulto , Bandagens , Corpos Estranhos/diagnóstico por imagem , Humanos , Masculino , Traumatismos Maxilofaciais/diagnóstico por imagem , Nariz/diagnóstico por imagem , Nariz/cirurgia , Tomografia Computadorizada por Raios X , Cicatrização , Ferimentos por Arma de Fogo/diagnóstico por imagem
13.
J Org Chem ; 74(4): 1557-66, 2009 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-19154130

RESUMO

Two bicyclic 2'-deoxynucleoside analogues are synthesized in 12 steps each from thymidine. With a six-membered ring fused to the C3'-C4' bond and an alpha-L-ribo- and a beta-D-xylo-configuration, these are conformationally restricted in an S- and an N-type conformation, respectively. The constitutions were proven by X-ray crystallography. The beta-D-xylo-configured analogue is successfully converted to a 3'-phosphoramidite and incorporated into oligodeoxynucleotides, which are found to hybridize to DNA and RNA complements with decreased affinity.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Nucleosídeos/síntese química , Ribose/química , Xilose/química , Sequência de Bases , Biomimética , Compostos Bicíclicos Heterocíclicos com Pontes/química , Configuração de Carboidratos , Cristalografia por Raios X , DNA/química , DNA/genética , DNA/metabolismo , Desnaturação de Ácido Nucleico , Nucleosídeos/química , Oligonucleotídeos/química , Oligonucleotídeos/genética , Oligonucleotídeos/metabolismo , RNA/química , RNA/genética , RNA/metabolismo , Estereoisomerismo , Especificidade por Substrato , Temperatura de Transição
14.
Artigo em Inglês | MEDLINE | ID: mdl-18776225

RESUMO

Two series of thymidine derivatives with additional nucleobases/aromatics attached to either the 5'(S)-C- or the 5-position were prepared by epoxide opening and/or "click chemistry" cycloaddition protocols and introduced into DNA duplexes. Interstrand base-base communication in the minor groove and intrastrand stacking interactions in the major groove were detected.


Assuntos
DNA/química , Timidina/análogos & derivados , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , Nucleosídeos de Pirimidina/síntese química , Nucleosídeos de Pirimidina/química , Temperatura , Triazóis/química
15.
Artigo em Inglês | MEDLINE | ID: mdl-18066892

RESUMO

Oligonucleotides containing 7-deaza-2'-deoxyxanthosine (1) and 2'-deoxyxanthosine (2) were prepared. The 2-(4-nitrophenyl)ethyl group is applicable for 7-deazaxanthine protection that is removed with DBU by beta-elimination, while the deprotection of the allyl residue with Pd (0) catalyst failed. Contrarily, the allyl group was found to be an excellent protecting group for 2'-deoxyxanthosine (2). The base pairing of nucleosides 1 and 2 with the four canonical DNA constituents as well as with 3 within the 12-mer duplexes is studied.


Assuntos
Pareamento de Bases , Desoxirribonucleosídeos/química , Nucleosídeos/química , Oligonucleotídeos/química , Compostos Organofosforados/síntese química , Compostos Organofosforados/química , Temperatura de Transição
16.
Org Biomol Chem ; 4(21): 3993-4004, 2006 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-17047881

RESUMO

Triplex-forming oligonucleotides (TFOs) containing 2'-deoxyisoguanosine (2), 7-bromo-7-deaza-2'-deoxyisoguanosine (2) as well as the propynylated 9-deazaguanine N7-(2'-deoxyribonucleoside) were prepared. For this the phosphoramidites 9a, b of the nucleoside 1 and, the phosphoramidites 19, 20 of compound 3b were synthesized. They were employed in solid-phase oligonucleotide synthesis to yield the protected 31-mer oligonucleotides. The deblocking of the allyl-protected oligonucleotides containing 1 was carried out by Pd(0)[PPh3]4-PPh3 followed by 25% aq. NH3. Formation of the 31-mer single-stranded intramolecular triplexes was studied by UV-melting curve analysis. In the single-stranded 31-mer oligonucleotides the protonated dC in the dCH(+)-dG-dC base triad was replaced by 2'-deoxyisoguanosine (1), 7-bromo-7-deaza-2'-deoxyisoguanosine (2) and, 9-deaza-9-propynylguanine N7-(2'-deoxyribonucleoside) (3b). The replacement of protonated dC by compounds 1 and 3b resulted in intramolecular triplexes which are formed pH-independently and are stable under neutral conditions. These triplexes contain "purine" nucleosides in the third pyrimidine rich strand of the oligonucleotide hairpin.


Assuntos
Citosina/química , DNA/química , DNA/síntese química , Guanina/análogos & derivados , Conformação de Ácido Nucleico , Prótons , Sequência de Bases , Cromatografia Líquida de Alta Pressão , DNA/genética , Guanina/síntese química , Guanina/química , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Peso Molecular , Oligonucleotídeos/síntese química , Oligonucleotídeos/química , Oligonucleotídeos/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Temperatura de Transição
17.
Acta Crystallogr C ; 62(Pt 5): o246-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16679593

RESUMO

In the title compound, 2'-deoxy-7-propynyl-7-deazaadenosine, C14H16N4O3, the torsion angle of the N-glycosylic bond is anti [chi = -130.7 (2) degrees ]. The sugar pucker of the 2'-deoxyribofuranosyl moiety is C2'-endo-C3'-exo, 2T3 (S-type), with P = 185.9 (2) degrees and tau(m) = 39.1 (1) degrees , and the orientation of the exocyclic C4'-C5' bond is -ap (trans). The 7-substituted propynyl group is nearly coplanar with the heterocyclic base moiety. Molecules of the nucleoside form a layered network in which the heterocyclic bases are stacked head-to-tail with a closest distance of 3.197 (1) A. The crystal structure of the nucleoside is stabilized by three intermolecular hydrogen bonds of types N-H... O, O-H... N and O-H... O.


Assuntos
DNA/química , Desoxiadenosinas/química , Cristalografia por Raios X , Ligação de Hidrogênio , Estrutura Molecular
18.
Org Biomol Chem ; 3(23): 4221-6, 2005 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-16294250

RESUMO

The stabilizing effect of 7-propynylated 7-deazapurine nucleosides on DNA-hairpins and DNA-duplexes containing d(GA) mismatches was investigated. The corresponding oligonucleotides were synthesized using solid-phase synthesis. For this purpose, the phosphoramidite of 7-deaza-7-propynyl-2'-deoxyadenosine (3c) was prepared. The incorporation of 3c instead of dA into the tandem d(GA) base pair of a DNA-hairpin alters the secondary structure, but has a positive effect on the duplex stability. A complete replacement of the canonical nucleosides of the tandem d(GA) base pair by 3c and 7-deaza-7-propynyl-2'-deoxyguanosine results in a significant base pair stabilization.


Assuntos
Pareamento de Bases , Desoxiadenosinas/química , Desoxiguanosina/análogos & derivados , Sequência de Bases , Dicroísmo Circular , Desoxiguanosina/química , Conformação de Ácido Nucleico , Termodinâmica
19.
Artigo em Inglês | MEDLINE | ID: mdl-16248048

RESUMO

Oligonucleotides containing 7-deazapurines or 9-deazapurines with propynyl groups at the 7- or 9-position were prepared. The stabilizing effect of the propynyl group was studied on DNA duplexes, hairpins and triplexes.


Assuntos
DNA/química , Ácidos Nucleicos Heteroduplexes/química , Purinas/química , Sequência de Bases , Modelos Químicos , Biologia Molecular/métodos , Dados de Sequência Molecular , Oligonucleotídeos/química , Oligonucleotídeos Antissenso/química , Compostos Organofosforados/química , Purinas/farmacologia , Temperatura , Termodinâmica
20.
Acta Crystallogr C ; 61(Pt 3): o151-3, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15750241

RESUMO

In the title compound, 2-amino-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, C11H14N4O4, the N-glycosylic bond torsion angle, chi, is anti [-106.5 (3) degrees ]. The 2'-deoxyribofuranosyl moiety adopts the 3T4 (N-type) conformation, with P = 39.1 degrees and tau(m) = 40.3 degrees . The conformation around the exocyclic C-C bond is ap (trans), with a torsion angle, gamma, of -173.8 (3) degrees . The nucleoside forms a hydrogen-bonded network, leading to a close-packed multiple-layer structure with a head-to-head arrangement of the bases. The nucleobase interplanar O=C-C...NH(2) distance is 3.441 (1) A.


Assuntos
Desoxiguanosina/análogos & derivados , Cristalografia por Raios X , Desoxiguanosina/química , Ligação de Hidrogênio , Estrutura Molecular , Conformação de Ácido Nucleico
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