Molecular detection of Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts in wild population of tsetse flies collected in Cameroon, Chad and Nigeria.

BACKGROUND: Tsetse flies are cyclical vectors of African trypanosomiasis (AT). The flies have established symbiotic associations with different bacteria that influence certain aspects of their physiology. Vector competence of tsetse flies for different trypanosome species is highly variable and is suggested to be affected by bacterial endosymbionts amongst other factors. Symbiotic interactions may provide an avenue for AT control. The current study provided prevalence of three tsetse symbionts in Glossina species from Cameroon, Chad and Nigeria. RESULTS: Tsetse flies were collected and dissected from five different locations. DNA was extracted and polymerase chain reaction used to detect presence of Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts, using species specific primers. A total of 848 tsetse samples were analysed: Glossina morsitans submorsitans (47.52%), Glossina palpalis palpalis (37.26%), Glossina fuscipes fuscipes (9.08%) and Glossina tachinoides (6.13%). Only 95 (11.20%) were infected with at least one of the three symbionts. Among infected flies, six (6.31%) had Wolbachia and Spiroplasma mixed infection. The overall symbiont prevalence was 0.88, 3.66 and 11.00% respectively, for Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts. Prevalence varied between countries and tsetse fly species. Neither Spiroplasma species nor S. glossinidius were detected in samples from Cameroon and Nigeria respectively. CONCLUSION: The present study revealed, for the first time, presence of Spiroplasma species infections in tsetse fly populations in Chad and Nigeria. These findings provide useful information on repertoire of bacterial flora of tsetse flies and incite more investigations to understand their implication in the vector competence of tsetse flies.

Sodalis glossinidius and Wolbachia infections in wild population of Glossina morsitans submorsitans caught in the area of Lake Iro in the south of Chad.

Investigations on the bacterial fauna and their association with trypanosome infections in tsetse fly have revealed contrasting results. This study aimed to detect Wolbachia and S. glossinidius in wild populations of G. m. submorsistans and subsequently, understand the influence that these bacteria may have on the vectorial competence of this tsetse species. Tsetse flies were captured in the area of Lake Iro in the south of Chad using biconical traps. After DNA extraction from each tsetse fly, Sodalis glossinidius and Wolbachia were detected using specific primers. Sodalis glossinidius and Wolbachia infection rates were compared and association studies involving trypanosome infections and S. glossinidius or Wolbachia were performed. From 345 G. m. submorsitans analyzed, 9.0% and 14.5% were respectively infected with S. glossinidius and Wolbachia. Only 2.31% of all tsetse flies were co-infected by the 2 bacteria. Of all trypanosome-infected flies, 7.1% and 9.8% harbored, respectively, S. glossinidius and Wolbachia. No association was observed between Wolbachia and trypanosome infections while a significant association (r = 4.992; P = 0.025) was found between S. glossinidius and the presence of trypanosomes. A significant association (r = 3.147; P = 0.043) was also observed between S. glossinidius and T. simiae; and none with T. congolense or T. godfreyi. This study revealed S. glossinidius and Wolbachia in G. m. submorsitans of the area of lake Iro. It showed that co-infections between Wolbachia and S. glossinidius are rare in wild populations of G. m. submorsitans and that the tripartite associations vary according to trypanosome species as well as symbiotic mricroorganisms.

Diversity and phylogenetic relationships of Glossina populations in Nigeria and the Cameroonian border region.

BACKGROUND: Tsetse flies are vectors of trypanosomes, parasites that cause devastating disease in humans and livestock. In the course of vector control programmes it is necessary to know about the Glossina species present in the study area, the population dynamics and the genetic exchange between tsetse fly populations. RESULTS: To achieve an overview of the tsetse fly diversity in Nigeria and at the Nigeria-Cameroon border, tsetse flies were trapped and collected between February and March 2014 and December 2016. Species diversity was determined morphologically and by analysis of Cytochrome C Oxidase SU1 (COI) gene sequences. Internal transcribed spacer-1 (ITS-1) sequences were compared to analyse variations within populations. The most dominant species were G. m. submorsitans, G. tachinoides and G. p. palpalis. In Yankari Game Reserve and Kainji Lake National Park, G. submorsitans and G. tachinoides were most frequent, whereas in Old Oyo National Park and Ijah Gwari G. p. palpalis was the dominant species. Interestingly, four unidentified species were recorded during the survey, for which no information on COI or ITS-1 sequences exists. G. p. palpalis populations showed a segregation in two clusters along the Cameroon-Nigerian border. CONCLUSIONS: The improved understanding of the tsetse populations in Nigeria will support decisions on the scale in which vector control is likely to be more effective. In order to understand in more detail how isolated these populations are, it is recommended that further studies on gene flow be carried out using other markers, including microsatellites.

SIGLEC-4 (MAG) Antagonists: From the Natural Carbohydrate Epitope to Glycomimetics.

Siglec-4, also known as myelin-associated glycoprotein (MAG), is a member of the siglec (sialic acid-binding immunoglobulin-like lectins) family. MAG binds with high preference to sialic acids α(2-3)-linked to D-galactose. Although the involvement and relevance of its sialic acid binding activity is still controversial, it could be demonstrated that interactions of MAG with sialylated gangliosides play an important role in axon stability and regeneration. In this article we describe in detail our current understanding of the biological role and the carbohydrate specificity of siglec-4. Furthermore, this review compiles the intensive research efforts leading from the identification of the minimal oligosaccharide binding epitope in gangliosides via micromolar oligosaccharide mimics to the development of small molecular weight and more drug-like sialic acid derivatives binding with low nanomolar affinities. Such compounds will be useful to elucidate MAG's biological functions, which are currently not fully understood.

The Transmission of Animal African Trypanosomiasis in Two Districts in the Forest Zone of Ghana.

Animal African trypanosomiasis, also known as nagana, is caused by Trypanosoma species, which cause significant clinical diseases and lead to losses in animal production. We carried out a cross-sectional survey to investigate the composition of vectors and parasite diversity in two districts in the eastern region of Ghana where pigs and cattle were exposed to tsetse bites. We performed cytochrome c oxidase subunit 1 polymerase chain reaction (PCR) to identify tsetse species and internal transcribed spacer 1 PCR to identify Trypanosoma species. Also, we investigated the source of tsetse blood meal based on mitochondrial cytochrome b gene sequence analysis. A total of 229 tsetse, 65 pigs, and 20 cattle were investigated for trypanosomes. An overall vector density of 4.3 tsetse/trap/day was observed. A trypanosome prevalence of 58.9% (95% CI = 52.5-65.1%), 46.2% (95% CI = 34.6-58.1%), and 0.0% (95% CI = 0.0-16.1%) in tsetse, pigs, and cattle, respectively, was detected. Trypanosoma congolense was predominant, with a prevalence of 33.3% (95% CI = 73.3-86.5%) in tsetse. There was evidence of multiple infections in tsetse and pigs. Approximately 39% of the tsetse were positive for multiple infections of T. congolense and Trypanosoma simiae. Parasite prevalence in pigs across the communities was high, with significant differences associated between locations (χ2 = 28.06, 95% CI = 0.05-0.81, P = 0.0009). Tsetse blood meal analysis revealed feeding on domestic Sus scrofa domesticus (pigs) and Phacochoerus africanus (warthogs). Infective tsetse may transmit trypanosomes to livestock and humans in the communities studied.

Molecular detection of Sodalis glossinidius, Spiroplasma and Wolbachia endosymbionts in wild population of tsetse flies collected in Cameroon, Chad and Nigeria.

Background Tsetse flies are cyclical vectors of African trypanosomiasis. They have established symbiotic associations with different bacteria, which influence certain aspects of their physiology. The vector competence of tsetse flies for different trypanosome species is highly variable and is suggested to be affected by various factors, amongst which are bacterial endosymbionts. Symbiotic interactions may provide an avenue for the disease control. The current study provided the prevalence of 3 tsetse symbionts in Glossina species from Cameroon, Chad and Nigeria. Results Tsetse flies were collected from five different locations and dissected. DNA was extracted and polymerase chain reaction PCR was used to detect the presence of Sodalis glossinidius , Spiroplasma sp and Wolbachia using specific primers. A total of 848 tsetse samples were analysed: Glossina morsitans submorsitans (47.52%), Glossina palpalis palpalis (37.26%), Glossina fuscipes fuscipes (9.08%) and Glossina tachinoides (6.13%). Only 95 (11.20%) were infected with at least one of the 3 symbionts. Among the infected, 6 (6.31%) were carrying mixed infection ( Wolbachia and Spiroplasma ). The overall symbiont prevalence was 0.88%, 3.66% and 11.00% respectively, for Sodalis , Spiroplasma and Wolbachia . Prevalence varied between countries and tsetse species. No Spiroplasma was detected in samples from Cameroon and no Sodalis was found in samples from Nigeria. Conclusion The present study revealed for the first time, the presence of infection by Spiroplasma in tsetse in Chad and Nigeria. These findings provide useful information to the repertoire of bacterial flora of tsetse flies and incite to more investigations to understand their implication in the vector competence of tsetse flies.

The association between leptin and inflammatory markers with obesity indices in Zanzibari children, adolescents, and adults.

BACKGROUND: Research from Western populations describes abdominal obesity as a low-grade inflammatory disease; less is known from tropical areas with high pathogen burden. OBJECTIVES: This cross-sectional study investigated whether obesity contributes to low-grade inflammation in 587 individuals from randomly selected households in Zanzibar. MATERIALS AND METHODS: The Association between obesity indices (body mass index [BMI], waist circumference [WC], and percentage body fat [%BF]), leptin, and inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6] and tumor-necrosis factor-α [TNF-α]) was investigated using multinomial logistic regression analysis, accounting for ordinal outcome variables with four categories; 1st-4th quartile. RESULTS: Study participants were between 5 and 95 years; 49.6% were male. Mean serum levels were; leptin: 4.3 ± 5.2 ng/ml, CRP: 0.19 ± 0.42 µg/ml, IL-6: 2.8 ± 5 pg/ml, and TNF-α: 5.3 ± 5.2 pg/ml. Obesity indices were associated with leptin and CRP in the third and fourth quartiles in single models. In combined models, associations were observed between BMI (OR = 6.36 [95% CI, 1.09; 34.12]); WC (OR = 4.87 [95% CI, 1.59; 14.94]); and %BF (OR = 19.23 [95% CI, 4.70; 78.66]) and leptin in the fourth quartile; also between %BF and CRP in the third quartile (OR = 3.49 [95% CI 1.31; 9.31]). CONCLUSION: Total body fat was associated with low-grade inflammation in this tropical population rather than body fat distribution such as abdominal obesity. This may increase the risk of insulin resistance and other obesity-related metabolic and cardiovascular health endpoints.

Diversity of tsetse flies and trypanosome species circulating in the area of Lake Iro in southeastern Chad.

BACKGROUND: African trypanosomiases are vector-borne diseases that affect humans and livestock in sub-Saharan Africa. Although data have been collected on tsetse fauna as well as trypanosome infections in tsetse flies and mammals in foci of sleeping sickness in Chad, the situation of tsetse fly-transmitted trypanosomes remains unknown in several tsetse-infested areas of Chad. This study was designed to fill this epidemiological knowledge gap by determining the tsetse fauna as well as the trypanosomes infecting tsetse flies in the area of Lake Iro in southeastern Chad. METHODS: Tsetse flies were trapped along the Salamat River using biconical traps. The proboscis and tsetse body were removed from each fly. DNA was extracted from the proboscis using proteinase K and phosphate buffer and from the tsetse body using Chelex 5%. Tsetse flies were identified by amplifying and sequencing the cytochrome c oxydase I gene of each tsetse fly. Trypanosome species were detected by amplifying and sequencing the internal transcribed spacer 1 of infecting trypanosomes. RESULTS: A total of 617 tsetse flies were trapped; the apparent density of flies per trap per day was 2. 6. Of the trapped flies, 359 were randomly selected for the molecular identification and for the detection of infecting trypanosomes. Glossina morsitans submorsitans (96.1%) was the dominant tsetse fly species followed by G. fuscipes fuscipes (3.1%) and G. tachinoides (0.8%). Four trypanosome species, including Trypanosoma vivax, T. simiae, T. godfreyi and T. congolense savannah, were detected. Both single infection (56.7%) and mixed infections of trypanosomes (4.6%) were detected in G. m. submorsitans. The single infection included T. simiae (20.5%), T. congolense savannah (16.43%), T. vivax (11.7%) and T. godfreyi (9.8%). The trypanosome infection rate was 61.4% in G. m. submorsitans, 72.7% in G. f. fuscipes and 66.6% in G. tachinoides. Trypanosome infections were more prevalent in tsetse bodies (40.6%) than in the proboscis (16.3%). CONCLUSION: This study revealed the presence of different tsetse species and a diversity of trypanosomes pathogenic to livestock in the area of Lake Iro. The results highlight the risks and constraints that animal African trypanosomiasis pose to livestock breeding and the importance of assessing trypanosome infections in livestock in this area.

The ligand-binding domain of CD22 is needed for inhibition of the B cell receptor signal, as demonstrated by a novel human CD22-specific inhibitor compound.

CD22 is a B cell-specific transmembrane protein of the Siglec family. It binds specifically to alpha2,6-linked sialic acid (Sia) residues, which are also present on glycoproteins on the B cell surface. CD22 acts as a negative regulator in B cell receptor-mediated signaling by recruitment of Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 to its intracellular tail. To analyze how ligand-binding of CD22 influences its intracellular signaling domain, we designed synthetic sialosides as inhibitors for the lectin domain of CD22. One of these compounds inhibited binding of human CD22-Fc to target cells over 200-fold better than Sia and was highly selective for human CD22. When Daudi cells or primary B cells were stimulated with anti-immunoglobulin (Ig)M in presence of this sialoside inhibitor, a higher Ca(2+) response was observed, similar to CD22-deficient B cells. Accordingly, a lower tyrosine-phosphorylation of CD22 and SHP-1 recruitment was demonstrated in presence of the sialoside. Thus, by interfering with ligand binding of CD22 on the B cell surface, we have shown for the first time that the lectin domain of CD22 has a direct, positive influence on its intracellular inhibitory domain. Also, we have developed a novel low molecular weight compound which can enhance the response of human B cells.

2-deoxyribose deprives cultured astrocytes of their glutathione.

High concentrations of 2-deoxy-D-ribose (2dRib) have been reported to cause oxidative stress and to disturb the glutathione (GSH) metabolism of various cell types. Exposure of astrocyte-rich primary cultures to millimolar concentrations of 2dRib or its stereoisomer 2-deoxy-L-ribose, but not the incubation with ribose, 2-deoxyglucose, glucose, fructose or saccharose, lowered the cellular GSH content in a time and concentration dependent manner. After exposure for 4 h to 30 mM 2dRib the cells contained 2dRib in a concentration of about 24 mM. Under these conditions 2dRib did not compromise cell viability and the ability of the cells to synthesise GSH, nor were the cellular ratio of glutathione disulfide (GSSG) to GSH and the extracellular concentrations of GSH or GSSG increased. These data demonstrate that 2dRib deprives viable cultured astrocytes of GSH and suggest that a cellular reaction of GSH with 2dRib or its metabolites is involved in the deprivation of astrocytic GSH.

Exploring Food Access and Sociodemographic Correlates of Food Consumption and Food Insecurity in Zanzibari Households.

Rapid growth of the Zanzibari population and urbanization are expected to impact food insecurity and malnutrition in Zanzibar. This study explored the relationship between food access (FA) and sociodemographic correlates with food consumption score and food insecurity experience scale. Based on cross-sectional data of 196 randomly selected households, we first investigated the association between sociodemographic correlates and Food Consumption Score (FCS) and Food Insecurity Experience Scale using multilevel Poisson regression. Secondly, the role of FA in these associations was investigated by interaction with the respective correlates. About 65% of households had poor food consumption, and 32% were severely food-insecure. Poor FA was more prevalent in households with poor food consumption (71%). Polygamous households and larger households had a higher chance for severe food insecurity. In the interaction with FA, only larger households with poor FA showed a higher chance for severe food insecurity. In households having no vehicle, good FA increased the chance of having acceptable FCS compared to poor FA. By contrast, urban households with good FA had a twofold chance of acceptable FCS compared to rural household with poor FA. Poor FA, poor food consumption and food insecurity are challenging; hence, facilitating households' FA may improve the population's nutrition situation.

Anthropometric and Biochemical Predictors for Hypertension in a Cross-Sectional Study in Zanzibar, Tanzania.

Background: Aim of this study was to describe the proportion of hypertension among Zanzibari of different age-groups and to detect possible correlates of this non-communicable disease. Methods: In 2013 a cross-sectional survey was conducted in Unguja Island, Zanzibar. A total of 235 randomly selected households, including 1,229 (2 to 95 years) eligible study participants, were examined. Association between objectively assessed obesity markers, salt intake and hypertension were investigated. Estimates of 24 h sodium and potassium excretion from a single morning spot urine specimen were calculated and used as surrogate for salt intake. The association between overweight/obesity and hypertension in different age-groups was assessed in multilevel logistic regression models. Further associations between salt intake and hypertension were analyzed. Results: Measures of systolic and diastolic blood pressure as well as proportion of overweight/obesity and hypertension both increased with age. Overweight and obesity were significantly associated with hypertension in adults. Moreover, thinness seems to be associated with hypertension as well. We observed a significantly reduced chance of hypertension for higher urinary sodium-to-potassium compared to a lower ratio in children. Conclusion: Overweight/obesity and hypertension were highly prevalent (>47% of adults >40 years are overweight or obese and >69% are hypertensive in the same age group) in our sample. Weight status was confirmed as a correlate of high blood pressure in our sample from Zanzibar, Tanzania. To early and effectively prevent related severe cardiovascular outcomes, screening strategies but also monitoring strategies are required for this population.

Association between cardiometabolic risk factors and body mass index, waist circumferences and body fat in a Zanzibari cross-sectional study.

OBJECTIVES: To determine the prevalence of obesity indices (body mass index (BMI), waist circumference (WC), body fat per cent (BF%)) and cardiometabolic risk factors. To investigate the association between obesity indices and cardiometabolic risk factors in a Zanzibari population. DESIGNS: Cross-sectional study. SETTINGS: Participants randomly selected from 80 Shehias (wards) in Unguja, Zanzibar in 2013. PARTICIPANTS: A total of 470 participants between 5 and 95 years were examined. Data on socioeconomic status, area of residence, anthropometry and venous blood were collected. Associations between obesity indices and cardiometabolic risk factors were investigated using multilevel logistic regression analyses in two steps: first, each obesity indicator was tested independently; second, all indicators combined in one model were tested for their association with cardiometabolic risk factors. RESULTS: The proportion of overweight/obese individuals was 26.4%, high WC (24.9%) and high BF% (31.1%). Cardiometabolic risk factors with highest prevalence of abnormal values included hypertension (24.5%), low high-density lipoprotein cholesterol (HDL-C) (29.4%), high low-density lipoprotein cholesterol (LDL-C) (21.3%) and high glycated haemoglobin (HbA1c) (19.1%). Obesity and hypertension increased with age, and were most prevalent in participants aged 45 years and above. Low HDL-C was most prevalent among participants aged ≥18 to <45 years, while high LDL-C was more prevalent in those above 45 years. High WC and high BF% were associated with high levels of LDL-C (OR=2.52 (95% CI 1.24 to 5.13), OR=1.91 (95% CI 1.02 to 3.58), respectively). Additionally, BMI and WC were associated with high levels of HbA1c (OR=2.08 (95% CI 1.15 to 3.79), OR=3.01 (95% CI 1.51 to 6.03), respectively). In the combined regression model, WC was associated with higher chances for hypertension (OR=2.62 (95% CI 1.14 to 6.06)) and for high levels of HbA1c (OR=2.62 (95% CI 1.12 to 6.15)). CONCLUSION: High BMI, WC and BF% were strongly associated with hypertension, with individuals with high WC being twice more likely to have hypertension; this calls for early and effective screening strategies for this study population.

Crystallographic and in silico analysis of the sialoside-binding characteristics of the Siglec sialoadhesin.

The Siglec family of receptors mediates cell-surface interactions through recognition of sialylated glycoconjugates. Previously reported structures of the N-terminal domain of the Siglec sialoadhesin (SnD1) in complex with various sialic acid analogs revealed the structural template for sialic acid binding. To characterize further the carbohydrate-binding properties, we have determined the crystal structures of SnD1 in the absence of ligand, and in complex with 2-benzyl-Neu5NPro and 2-benzyl-Neu5NAc. These structures reveal that SnD1 undergoes very few structural changes on ligand binding and detail how two novel classes of sialic acid analogs bind, one of which unexpectedly can induce Siglec dimerization. In conjunction with in silico analysis, this set of structures informs us about the design of putative ligands with enhanced binding affinities and specificities to different Siglecs, and provides data with which to test the effectiveness of different computational drug design protocols.

The structure of siglec-7 in complex with sialosides: leads for rational structure-based inhibitor design.

Siglecs (sialic acid binding Ig-like lectins) are transmembrane receptors for sialylated glycoconjugates that modulate cellular interactions and signalling events in the haematopoietic, immune and nervous systems. Siglec-7 is a structural prototype for the recently described family of immune inhibitory CD33-related siglecs and is predominantly expressed on natural killer cells and monocytes, as well as subsets of CD8 T-cells. Siglec-specific inhibitors are desired for the detection of masked and unmasked forms of siglecs, to aid in dissection of signalling pathways and as tools to investigate siglecs as potential therapeutic targets. As a first step towards this end, we present the crystal structure of siglec-7 in complex with a sialylated ligand, the ganglioside analogue DSLc4 [alpha(2,3)/alpha(2,6) disialyl lactotetraosyl 2-(trimethylsilyl)ethyl], which allows for a detailed description of the binding site, required for structure-guided inhibitor design. Mutagenesis and binding assays were used to demonstrate a key structural role for Lys131, a residue that changes conformation upon sialic acid binding. Differences between the binding sites of siglec family members were then exploited using alpha-methyl Neu5Ac (N-acetylneuraminic acid) as a basic scaffold. A co-crystal of siglec-7 in complex with the sialoside inhibitor, oxamido-Neu5Ac [methyl alpha-9-(amino-oxalyl-amino)-9-deoxy-Neu5Ac] and inhibition data for the sialosides gives clear leads for future inhibitor design.

Design, Response Rates, and Population Characteristics of a Cross-Sectional Study in Zanzibar, Tanzania.

BACKGROUND: Data on nutritional status and correlates of noncommunicable diseases are scarce for resource-poor settings in sub-Saharan countries. With the scope of a project, "Access to Food and Nutrition Status of the Zanzibari Population," data for investigating public health questions were collected using proven measurement and laboratory standards. OBJECTIVE: The present study aims at providing a descriptive overview of recruitment approaches, standardization, quality control measures, and data collection, with special attention to the design, responses, and participant characteristics of the overall project. METHODS: A cross-sectional study across 80 randomly selected Shehias (wards) was conducted in 2013 in Unguja Island, Zanzibar. Examinations included all members living in 1 household, face-to-face interviews and anthropometric measurements (weight, height, mid-upper arm circumference, waist and hip circumference, and body composition) were assessed for all household members, blood pressure was taken from participants older than 2 years, and biosamples (urine and blood) from eligible household members were collected. Data collected from the core sample included sociodemographic data, nutritional status, and medical history (hypertension). Physical activity data was collected from a subsample of children between 3 and 16 years of age. RESULTS: A total of 1314 participants (mean age 23.6 ± 18.9 years, 54.54% female) completed all anthropometric measurements and were included in the analysis. Out of which, 98.40% (1293/1314) completed the household member's questionnaire, 93.32% (1229/1314) participants older than 2 years completed blood pressure measurements, and 64.31% (845/1314) blood samples were collected from participants older than 5 years. Underweight prevalence for the total study population was 36.53% (480/1314) with the highest prevalence in children under 14 years. Overweight and obesity was highest among females with the prevalence of 7.61% (100/1314) and 6.62% (87/1314), respectively; obesity was rare among male participants. CONCLUSIONS: The study provides valuable data to investigate the interplay of socioeconomic, demographic, environmental, physiological, and behavioral factors in the development of diet-related disorders in a representative sample of the Zanzibari population.

Kinetic and thermodynamic properties of MAG antagonists.

Paraplegia is caused by injuries of the central nervous system (CNS) and especially young people suffer from these severe consequences as, for example, the loss of motor functions. The lack of repair of the injured nerve strands originates from the inhibitory environment for axon regeneration in the CNS. Specific inhibitory proteins block the regrowth of nerve roots. One of these neurite outgrowth inhibitors is the myelin-associated glycoprotein (MAG), which is a member of the Siglec family (sialic acid-binding immunoglobulin-like lectin). In previous studies, we identified potent small molecule MAG antagonists. In this communication, we report new neuraminic acid derivatives modified in the 4- and 5-position, and the influence of various structural modifications on their kinetic and thermodynamic binding properties.