Psychometric properties of the Beliefs About Adults with ID Scale in American physicians: Application of classical test and Rasch measurement theories.

BACKGROUND: Physicians' erroneous assumptions about individuals with intellectual disability (ID) negatively impact the quality of care provided to this population. This study aimed to investigate the psychometric properties of the Beliefs About Adults with ID (BAID), an instrument we developed for measuring physicians' erroneous assumptions about adults with ID. METHODS: Two hundred ninety-two American physicians participated. Classical test theory and Rasch measurement theory were used to refine the scale (through item analysis, exploratory factor analysis, infit and outfit mean-squares statistics, and differential item functioning) and investigate its psychometric properties (functioning of the response scale, reliability, and validity). RESULTS: The BAID provided a unidimensional, reliable, valid, and precise measure in assessing high levels of erroneous assumptions. It showed convergent and divergent validity with the different factors of a scale measuring attitudes towards ID. The BAID items were discriminant, non-redundant, unambiguous, and invariant across gender and previous ID training. The BAID response scale was found to be appropriate for measuring physicians' erroneous assumptions about adults with ID. CONCLUSIONS: BAID is a brief instrument with good psychometric properties to assess erroneous assumptions about adults with ID in physicians of different genders and who have/have not previously received ID training. Therefore, it might be helpful for research and medical education purposes.

A new measure of physicians' erroneous assumptions towards adults with intellectual disability: A first study.

BACKGROUND: Incomplete knowledge and unfamiliarity with intellectual disability (ID) contribute to erroneous assumptions of physicians towards ID, which negatively impact the health equity of people with ID. This study aimed to identify the erroneous assumptions that, based on the ID stakeholders' perceptions, were the most prevalent in physicians and damaging for the healthcare of adults with ID, verify their unidimensionality and that no personal characteristics of ID stakeholders were associated with their ratings of erroneous assumptions' prevalence and damage. METHODS: Seventy-four possible physician erroneous assumptions were developed concerning health, daily living skills and quality of life of individuals with ID. ID stakeholders rated each one for perceived prevalence in physicians and damage for the healthcare of adults with ID. Frequency analysis, exploratory factor analysis and correlations were run separately for participants' prevalence and damage ratings. RESULTS: Twenty-seven erroneous assumptions were identified as those perceived most prevalent and damaging. Their unidimensionality was ascertained and participants' characteristics were not associated with their prevalence and damage ratings. CONCLUSIONS: The identified assumptions are appropriate to represent the items of a new instrument that can be used in medical education to guide the development of curricula to change erroneous assumptions.

Developing behavioural indicators for intellectual functioning and adaptive behaviour for ICD-11 disorders of intellectual development.

BACKGROUND: We present the work conducted to arrive at deriving behavioural indicators that could be used to guide clinical judgement in determining the presence and severity of deficits in intellectual functioning and adaptive behaviour for the purpose of making a diagnosis of disorders of intellectual development. METHODS: An interdisciplinary expert panel provided guidance in developing behavioural indicators for intellectual functioning. A national dataset of adaptive behaviour on a sample of individuals with a diagnosis of intellectual disability was used to develop the behavioural indicators for the adaptive behaviour. The adaptive behaviour data were analysed using a cluster analysis procedure to define the different severity groupings by chronological age groups. RESULTS: We present a series of tables containing behavioural indicators across the lifespan for intellectual functioning and adaptive behaviour, including conceptual, social and practical skills. These tables of behavioural indicators have been proposed for use in the clinical version of the 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11) to be published by the World Health Organization. CONCLUSIONS: The proposed behavioural indicators for disorders of ID described in the present article and to be included in the ICD-11 Clinical Descriptions and Diagnostic Guidelines are put forth to assist professionals in making an informed clinical decision regarding an individual's level of intellectual functioning and adaptive behaviour for the purpose of making a determination about the presence and severity of disorders of ID.

Validity and reliability of the Diagnostic Adaptive Behaviour Scale.

BACKGROUND: The Diagnostic Adaptive Behaviour Scale (DABS) is a new standardised adaptive behaviour measure that provides information for evaluating limitations in adaptive behaviour for the purpose of determining a diagnosis of intellectual disability. This article presents validity evidence and reliability data for the DABS. METHOD: Validity evidence was based on comparing DABS scores with scores obtained on the Vineland Adaptive Behaviour Scale, second edition. The stability of the test scores was measured using a test and retest, and inter-rater reliability was assessed by computing the inter-respondent concordance. RESULTS: The DABS convergent validity coefficients ranged from 0.70 to 0.84, while the test-retest reliability coefficients ranged from 0.78 to 0.95, and the inter-rater concordance as measured by intraclass correlation coefficients ranged from 0.61 to 0.87. CONCLUSIONS: All obtained validity and reliability indicators were strong and comparable with the validity and reliability coefficients of the most commonly used adaptive behaviour instruments. These results and the advantages of the DABS for clinician and researcher use are discussed.

PC1, a non-peptide PKR1-preferring antagonist, reduces pain behavior and spinal neuronal sensitization in neuropathic mice.

Peripheral neuropathy is characterized by abnormal pain responses triggered by the release of several mediators and neuronal hyperexcitability at the spinal cord level. Emerging evidence indicates that the enhanced activity of dorsal horn neurons requires communication with glia and microglia, cells that are physiologically involved in neuronal wellbeing. Prokineticins (PKs), which include PK1 and PK2, represent a novel family of chemokines characterized by a unique structural motif comprising five disulfide bonds. They are expressed in the peripheral and central nervous system. PKs bind two G protein coupled receptors, PKR1 and PKR2, and participate in the regulation of several biological processes, including pain sensation. This study aimed to investigate the anti-nociceptive effect of PC1, a non-peptide PKR1-preferring antagonist, in a mouse model of neuropathic pain. To do this, we assessed the activity of spinal cord nociceptive neurons as well as astrocyte and microglia phenotypes after repeated administration of PC1 in vivo. PC1 treatment strongly delayed the development of thermal hyperalgesia and tactile and mechanical allodynia. It also reduced spinal microglial and glial activation 8 days post injury in spared nerve injury (SNI) mice. Neuropathic mice showed an increased level of PK2 protein in the spinal cord, mostly in astrocytes. PC1 treatment completely reversed the increased responsiveness to mechanical stimuli, the decreased threshold of neuronal activation, and the increased spontaneous activity that were observed in nociceptive specific (NS) neurons of SNI mice.

Controlling the activation of the Bv8/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals.

BACKGROUND AND PURPOSE: Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2 ) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain. EXPERIMENTAL APPROACH: Effects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve (CCI). Expression and localization of PROK2 and of its receptors at peripheral and central level was evaluated 10 days after CCI, following treatment for 1 week with saline or PC1. IL-1ß and IL-10 levels, along with glia activation, were evaluated. KEY RESULTS: Subcutaneous, intrathecal and perineural PC1 acutely abolished the CCI-induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor PKR2 were up-regulated in nociceptors, in Schwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury-induced overexpression of PROK2, significantly blunted nerve injury-induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti-inflammatory cytokines in periphery and in spinal cord. CONCLUSION AND IMPLICATIONS: The prokineticin system contributes to pain modulation via neuron-glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.

Antidepressant-like and anxiolytic-like effects following activation of the µ-δ opioid receptor heteromer in the nucleus accumbens.

Treatment-resistant major depressive disorder remains inadequately treated with currently available antidepressants. Opioid receptors (ORs) are involved in the pathophysiology of depression yet remain an untapped therapeutic intervention. The µ-δ OR heteromer represents a unique signaling complex with distinct properties compared with µ- and δ-OR homomers; however, its role in depression has not been characterized. As there are no ligands exclusively targeting the µ-δ heteromer, we devised a strategy to selectively antagonize the function of the µ-δOR complex using a specific interfering peptide derived from the δOR distal carboxyl tail, a sequence implicated in µ-δOR heteromerization. In vitro studies using a minigene expressing this peptide demonstrated a loss of the unique pharmacological and trafficking properties of δ-agonists at the µ-δ heteromer, with no effect on µ- or δ-OR homomers, and a dissociation of the µ-δOR complex. Intra-accumbens administration of the TAT-conjugated interfering peptide abolished the antidepressant-like and anxiolytic-like actions of the δ-agonist UFP-512 (H-Dmt-Tic-NH-CH(CH2-COOH)-Bid) measured in the forced swim test, novelty-induced hypophagia and elevated plus maze paradigms in rats. UFP-512's antidepressant-like and anxiolytic-like actions were abolished by pretreatment with either µOR or δOR antagonists. Overall, these findings demonstrate that the µ-δ heteromer may be a potential suitable therapeutic target for treatment-resistant depression and anxiety disorders.

Agonists at the δ-opioid receptor modify the binding of µ-receptor agonists to the µ-δ receptor hetero-oligomer.

BACKGROUND AND PURPOSE: µ- and δ-opioid receptors form heteromeric complexes with unique ligand binding and G protein-coupling profiles linked to G protein α z-subunit (Gα(z) ) activation. However, the mechanism of action of agonists and their regulation of the µ-δ receptor heteromer are not well understood. EXPERIMENTAL APPROACH: Competition radioligand binding, cell surface receptor internalization in intact cells, confocal microscopy and receptor immunofluorescence techniques were employed to study the regulation of the µ-δ receptor heteromer in heterologous cells with and without agonist exposure. KEY RESULTS: Gα(z) enhanced affinity of some agonists at µ-δ receptor heteromers, independent of agonist chemical structure. δ-Opioid agonists displaced µ-agonist binding with high affinity from µ-δ heteromers, but not µ receptor homomers, suggestive of δ-agonists occupying a novel µ-receptor ligand binding pocket within the heteromers. Also, δ-agonists induced internalization of µ-opioid receptors in cells co-expressing µ- and δ-receptors, but not those expressing µ-receptors alone, indicative of µ-δ heteromer internalization. This dose-dependent, Pertussis toxin-resistant and clathrin- and dynamin-dependent effect required agonist occupancy of both µ- and δ-opioid receptors. In contrast to µ-receptor homomers, agonist-induced internalization of µ-δ heteromers persisted following chronic morphine exposure. CONCLUSIONS AND IMPLICATIONS: The µ-δ receptor heteromer may contain a novel δ-agonist-detected, high-affinity, µ-receptor ligand binding pocket and is regulated differently from the µ-receptor homomer following chronic morphine exposure. Occupancy of both µ- and δ-receptor binding pockets is required for δ-agonist-induced endocytosis of µ-δ receptor heteromers. δ-Opioid agonists target µ-δ receptor heteromers, and thus have a broader pharmacological specificity than previously identified.

Na+ mechanism of delta-opioid receptor induced protection from anoxic K+ leakage in the cortex.

Activation of delta-opioid receptors (DOR) attenuates anoxic K(+) leakage and protects cortical neurons from anoxic insults by inhibiting Na(+) influx. It is unknown, however, which pathway(s) that mediates the Na(+) influx is the target of DOR signal. In the present work, we found that, in the cortex, (1) DOR protection was largely dependent on the inhibition of anoxic Na(+) influxes mediated by voltage-gated Na(+) channels; (2) DOR activation inhibited Na(+) influx mediated by ionotropic glutamate N-methyl-D-aspartate (NMDA) receptors, but not that by non-NMDA receptors, although both played a role in anoxic K(+) derangement; and (3) DOR activation had little effect on Na(+)/Ca(2+) exchanger-based response to anoxia. We conclude that DOR activation attenuates anoxic K(+) derangement by restricting Na(+) influx mediated by Na(+) channels and NMDA receptors, and that non-NMDA receptors and Na(+)/Ca(2+) exchangers, although involved in anoxic K(+) derangement in certain degrees, are less likely the targets of DOR signal.

In vitro and in vivo pharmacological profile of UFP-512, a novel selective delta-opioid receptor agonist; correlations between desensitization and tolerance.

BACKGROUND AND PURPOSE: Delta-opioid receptors (DOP receptors) could represent a novel target in the treatment of depressive disorders. To explore this new field of interest, the development of highly selective DOP receptor agonists is essential. UFP-512 [H-Dmt-Tic-NH-CH(CH2-COOH)-Bid], was recently shown to behave in vitro as a selective and potent DOP receptor agonist and to promote antidepressant- and anxiolytic-like effects in vivo (Vergura et al., 2007). Here, we have characterized the pharmacological properties of UFP-512 and established a link between desensitization and tolerance. EXPERIMENTAL APPROACH: Studies were performed in the human neuroblastoma SK-N-BE cells to establish i) binding parameters for UFP-512 ii) signalling pathways activated after acute and chronic treatment iii) regulation (phosphorylation and trafficking) of human DOP (hDOP) receptors after sustained activation by UFP-512. In vivo, we studied UFP-512-induced antidepressant-like effects after acute or chronic treatment in the mouse forced swimming test. KEY RESULTS: In vitro, UFP-512 was a high affinity agonist for DOP receptors. While UFP-512 induced marked phosphorylation of DOP receptors on Ser363, we observed a low desensitization of the cAMP pathway, associated with receptor endocytosis and recycling without any reduction on extracellular signal-regulated protein kinase 1/2 activation. In vivo, acute administration of UFP-512 produced an antidepressant-like effect, without any sign of tolerance after chronic administration. CONCLUSIONS AND IMPLICATIONS: There was a correlation between weak desensitization, significant internalization and recycling of the human DOP receptors and lack of tolerance to UFP-512. This suggests that this compound would be a promising drug prototype for exploring innovative treatments for mood disorders.

Cross-cultural study of person-centred quality of life domains and indicators: a replication.

BACKGROUND: The increased use of the quality of life (QOL) concept internationally suggests the need to evaluate its etic (universal) and emic (culture-bound) properties. This study replicated and expanded a previous cross-cultural study on QOL. METHOD: The three respondent groups (consumers, parents and professionals; total n = 781) were from four European countries: France, Belgium, Italy and Poland. The Cross Cultural Survey of Quality of Life Indicators was used to assess the importance and use of eight core dimensions of QOL. Two hypotheses were tested: (1) the etic properties would be demonstrated if there were similar profiles for the respondent and geographical groups, and if indicators grouped into the proposed QOL domains; and (2) the emic properties would be demonstrated if there were significant differences on scores across groups. RESULTS: Results supported both hypotheses. CONCLUSION: The present study replicated the findings of a large cross-cultural study that the QOL construct has both etic and emic properties.

Design, synthesis, DNA binding, and biological evaluation of water-soluble hybrid molecules containing two pyrazole analogues of the alkylating cyclopropylpyrroloindole (CPI) subunit of the antitumor agent CC-1065 and polypyrrole minor groove binders.

We have synthesized and evaluated a series of hybrids, denoted 22--27, for in vitro cytotoxic activity against a variety of cancer cell lines. These hybrids represent a molecular combination of polypyrrole minor groove binders structurally related to the natural antitumor agent distamycin A and two pyrazole analogues of the left-hand segment called cyclopropylpyrroloindole (CPI) of the potent antitumor antibiotic (+)-CC-1065. These novel water-soluble hybrids have been designed to enhance the minor groove binding ability of alkylating units 20 and 21, which should increase their clinical appeal by overcoming the administration problems of (+)-CC-1065 derivatives. The DNA alkylating and cytotoxic activities against several tumor cell lines are reported and discussed in terms of their structural differences in relation to both the number of N-methyl pyrrole rings and the type of the alkylating unit tethered to the oligopeptidic frame. It may be noted that, in general, and especially for 22--24, the cytotoxicity of the hybrids was much greater than that of the alkylating units alone. In only one case, compound 27, did the hybrid have cytotoxic activity comparable to that of the alkylating unit alone against FM3A/0 cells. The broadest spectrum of activity and greatest potency was shown by the hybrid 24, in which the alkylating unit 20 and the deformyl distamycin A are tethered by 1-methyl 2,5-dicarbonyl pyrazole, with IC(50) values for the different tumor cell lines ranging from 7 to 71 nM. For compounds 22--24, the increase of the length of the pseudopeptidic moiety from one to three N-methylpyrrole residues led to an increased cytotoxicity. Among the hybrids tested for their inhibitory effects on the proliferation of murine L1210 leukemia cell line, compound 24 proved to be the most active (IC(50) = 7.4 nM), and in the sequencing gel experiments, it showed the strongest and most highly sequence-specific DNA alkylation activity. For compounds 22-24, the sequence specificity of DNA alkylation appears to be affected by the modification of the number of pyrrole rings, and the correlation between cytotoxicity and alkylation pattern suggests that 24 exerts its cytotoxicity through DNA sequence-specific alkylation of the third adenine located in the sequence 5'-ACAAAAATCG-3'. The two other hybrids 22 and 23 were slightly less active for tumor cell proliferation, with IC(50) values of 58 and 19 nM, respectively. With only one exception, none of the compounds was endowed with antiviral activity at subtoxic concentrations. Compound 24 inhibited the effect of vaccinia virus at a concentration that was significantly lower than its minimum cytotoxic concentration for the E(6)SM host cells. These compounds gave distinct patterns of alkylation in AT-rich sequences, indicating that minor structural changes produced marked alterations in sequence selectivity.

Inhibition of human multidrug resistance P-glycoprotein 1 by analogues of a potent delta-opioid antagonist.

Analogues Dmt-Tic (2',6'-dimethyl-L-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) pharmacophore, a potent delta-opioid receptor antagonist, inhibited hMDR1 P-GP expressed in a G-185 fibroblast cell line in a manner similar to verapamil. N,N(Me)2-Dmt-Tic-NH-1-adamantane, H-Dmt-Tic-NH-1-adamantane, H-Dmt-Tic-Ala-NH-1-adamantane and N,N(Me)2-Dmt-Tic-NH-tBut were highly effective inhibitors. Weaker inhibition was observed with N,N(Et)2-Dmt-Tic-OH, H-Dmt-Tic-Ala-NH-tert-butyl amide and cyclo(Dmt-Tic). Results demonstrate that N- and C-terminal hydrophobic/lipophilic analogues of the Dmt-Tic pharmacophore inhibit hMDR1 and point to a potential role as chemosensitizing agents in chemotherapy for cancers containing hMDR1.

Discriminant validity of the Vineland Scales: score profiles of individuals with mental retardation and a specific disorder.

Utility of the Vineland Adaptive Behavior Scales-Expanded Form to discriminate among areas of adaptive behavior was substantiated by comparing profiles of scores obtained by three groups of individuals with mental retardation and either a communication, social behavior, or motor abilities disorder with those of matched individuals with mental retardation but no other disorder. Individuals with social behavior disorders obtained lower scores only in the Socialization domain; those with motor disorders, in the Motor domain and in the Personal and Domestic subscales that require motor competencies; and those with communication disorders, lower scores in the Communication domain and in the Community and Interpersonal Relationships subscales requiring expressive competencies. The utility of the Vineland Scales in obtaining an ecological evaluation of individuals with mental retardation is discussed.

Opioid pseudopeptides containing heteroaromatic or heteroaliphatic nuclei.

In lieu of H-Dmt-Tic-OH, H-Dmt-analogues included 2-amino-3(1H-benzoimidazol-2-yl)-propionic acid, N(Bzl)Gly, L-octahydroindole-2-carboxylic acid, [3S-(3alpha,4abeta, 8abeta)]-decahydro-3-isoquinoline carboxylic acid, benzimidazole-, pyridoindole- or spiroinden-derivatives, or C-terminally modified. L- or D-Ala, Sar, or Pro were spacers between aromatic nuclei. Only H-Dmt-(Xaa-)-pyridoindole exhibited high affinities with delta and mu antagonism. The peptides competed equally against [3H]DPDPE (delta agonist) or [3H]N,N(CH3)2-Dmt-Tic-OH (delta antagonist) signaling a single delta binding site. The data confirm the importance of Tic for delta affinity and antagonism, while heterocyclic or heteroaliphatic nuclei, or spacer exert effects on mu- and delta-receptor properties.

Inverse agonism by Dmt-Tic analogues and HS 378, a naltrindole analogue.

The potent delta-opioid receptor antagonist H-2',6-L-tyrosine(Dmt)-1, 2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic-OH) exhibited partial inverse agonism (EC(50)=6.35 nM, E(max)=-18.87%) for [35S]GTPgammaS binding and H-Dmt-Tic-NH(2) was a neutral antagonist (no effect up to 30 microM). In contrast N,N(CH(3))(2)-Dmt-Tic-NH(2) was a full inverse agonist (EC(50)=2.66 nM, E(max)=-35.95%) similar to ICI 174864 ([N,N-diallyl-Tyr(1),Aib(2,3),Leu(5)]enkephaline) but with a 3.5-fold higher EC(50). In comparison, naltrindole was a neutral antagonist while its analogue HS 378 was a partial inverse agonist (E(max)=-12.99%).

The psychopathology inventory for mentally retarded adults: factor structure and comparisons between subjects with or without dual diagnosis.

Whether the Psychopathology Inventory for Mentally Retarded Adults (PIMRA) could detect specific psychopathological disorders was investigated in 652 subjects with different levels of mental retardation living in the community or in residential facilities. An exploratory factor analysis was carried out to check the scale organization of PIMRA. The Anxiety, Adjustment Disorder, Somatoform Disorder, and Soundness Scales were confirmed by 4 corresponding factors; the Psychosexual Disorder Scale was replaced by a factor specific to gender identity problems, and the Schizophrenia Scale by two factors concerning isolation and bizarre behaviors, respectively. The items of the Depression Scale were distributed over the three factors concerning anxiety, adjustment, and psychosomatic disorders, while the items of the Personality Disorder Scale were scattered over almost all the factors. Moreover, 55 subjects with anxiety disorders and 49 with depression were compared to 50 control subjects of the same age, intelligence level, and gender ratio but without dual diagnosis and obtained significantly higher factorial scores both on the overall scale and on the factors specifically related to their disorders. PIMRA has been found to show good construct validity. These results could be considered particularly valid as they were obtained from a large sample comprising different levels of mental retardation and thus showing all possible psychopathological behaviors.

Synthesis and binding of 3-aminopyridine derivatives at central nicotinic receptors.

A series of secondary and tertiary pyridyl amides as potential central nicotinic acetylcholine receptors (nAChRs) ligands were prepared. Amides displayed negligible or very low affinity, whereas two amines achieved by reduction of corresponding secondary amides, showed affinity in the nanomolar range for nAChRs.

Characterization of N,N(Me)2-Dmt-Tic-OH, a delta selective opioid dipeptide antagonist.

N,N(Me)2-Dimethyl-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-OH (N,N(Me)2-Dmt-Tic-OH) is a very selective delta opioid dipeptide with elevated antagonist activity. We have radiolabelled this compound by catalytic tritiation of the N,N(Me)2-Dmt(3',5'-I2)-Tic-OH precursor. The ligand labelled rat brain membranes with a Kd value of 0.42 nM and a Bmax of 63.12 fmol/mg protein. The new tritiated ligand showed high affinity for the delta opioid receptor whereas its binding at mu and kappa opioid receptors was weak. N,N(Me)2-Dmt-Tic-OH was able to inhibit the agonist-stimulated binding of the non-hydrolysable GTP analogue ¿35SGTPgammaS, thus attenuating the activation of G proteins via opioid receptors. This simple opioid dipeptide in both normal and labelled form may serve as a useful tool to study delta opioid receptors in vitro and in vivo.

Effect of lysine residues on the deamidation reaction of asparagine side chains.

The effect of lysine residues on the deamidation reaction of the asparagine side chain has been studied on the peptide and on its lysine-acetylated derivative in a wide range of pH values. The amino acid sequence of these peptides is similar to the local sequence flanking the labile Asn-67 in RNAse A. The experimental data show that Lys influences both the deamidation rate and the relative yield of the two reaction products, i.e., the aspartic acid and beta-aspartic acid containing peptide. These effects are pH dependent and can be rationalized based on the mechanism previously proposed for the deamidation reaction via succinimide derivative.