Because there are many known C-terminally amidated peptides of biological importance, there is great potential in medicine and organic synthesis for antibodies that catalyze primary amide bond hydrolysis or formation. We characterized a catalytic antibody, 13D11, raised to a phosphinate hapten, that hydrolyzed the primary amide of a dansyl-alkylated derivative of (R)-phenylalaninamide (DNS-(R)F-NH2). At pH 9.0, 13D11 hydrolyzed DNS-(R)F-NH2 with a kcat of 1.65 x 10(-7) s-1 (kcat/kuncat = 132) and a Km of 432 microM, and was stereospecifically hapten-inhibited (Ki = 14.0 microM). Control experiments indicated that the catalytic activity was not the result of a contaminating protease. In accordance with the hapten being a transition-state analog of base hydrolysis, the rate of DNS-(R)F-NH2 hydrolysis increased with hydroxide concentration to an optimum pH of 9.5. Above pH 9.5, activity declined rapidly suggesting the antibody was inactivated during the long incubation period. This work demonstrates the feasibility of generating catalytic antibodies to hydrolyze unactivated amide bonds without cofactor assistance.

Amides↗

PubMedDate not supplied

Weight gain from novel antipsychotic drugs: need for action.

Obesity is common in schizophrenia, and people with schizophrenia appear to be at increased risk for certain obesity-related conditions, such as type 2 diabetes and cardiovascular disease. Antipsychotic drugs, used chronically to control symptoms of schizophrenia, are associated with often-substantial weight gain, a side effect that is a special concern with the latest generation of highly effective "novel" agents. That the most effective (e.g., novel) antipsychotic medications lead to substantial weight gain presents the field with a critical public health problem. Although preliminary data have been reported regarding the beneficial use of behavior therapy programs for short-term weight control in patients with schizophrenia, the available data are quite limited, and there are no data regarding the long-term beneficial effects of these programs in this population. The obesity field recently has developed programs emphasizing "lifestyle changes" (e.g., diet, exercise, and problem-solving skills) to successfully manage weight in patients without schizophrenia. Such programs can be adapted for patients with schizophrenia through the use of highly structured and operationalized modules emphasizing medication compliance, social skills development, and participation in outpatient programs. Moreover, these programs can potentially be combined with the use of adjunctive pharmacotherapy to maximize and maintain weight loss. The field must solve the paradox that some of our most effective medications for schizophrenia produce substantial weight gain and its associated troubling health risks.

Antipsychotic Agents↗

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Obesity and cardiovascular disease risk: research update.

The obesity epidemic has reached unprecedented proportions in Western society. Evidence continues to accumulate that obesity is associated with significant morbidity and mortality and in particular that it is an independent risk factor for cardiovascular disease (CVD). The association of obesity with CVD and its risk factors, including hypertension, dyslipidemia, glucose intolerance, and impaired hemostasis is becoming more clearly understood. An increasing body of data indicates that risk factors tend to cluster in obese individuals and may act synergistically to increase these people's risk for CVD. Individuals with disproportionate visceral adiposity are at significantly greater risk for CVD. Adult weight gain also underlies the development of many risk factors and augments the risk of CVD. Physicians can play a vital and active role in the prevention and treatment of obesity and overweight and thereby reduce patients' CVD risk.

Cardiovascular Diseases↗

PubMedDate not supplied

Total parenteral nutrition: physician and lifeliner.. Interview by Phillip Pressel.

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Female↗