Peptide hormones, design

In light of the importance of the / -turn motif in peptide and protein recognition, and the design and synthesis of bioactive small molecules, / -turn mimetics has attracted considerable attention. Seebach and coworkers have shown recently that low molecular weight open-chain / - and y-peptides designed to promote turn formation can be used as templates for mimicking the a-peptide hormone somatostatin. 

In an effort to overcome some of these difficulties and to provide the beginnings of a rational approach to the design of hormone analogs, we have utilized conformational and topographical restriction of peptide hormone and neurotransmitter structures. In this approach, we have attempted to make use where possible of classical structure-function studies, to Interpret the results from these studies In terms of specific conformational parameters which may be Involved In the observed rela-... 

In addition, any rational approach to peptide hormone and neurotransmitter design must ultimately depend on the application of physical-chemical principles of conformation and structure, the use of various spectroscopic methods (especially nuclear magnetic resonance, circular dlchrolsm, and Raman spectroscopies. X-ray analysis where possible, etc.), and an understanding of the nature of a hormone-receptor Interaction In physical-chemical terms. Here again the use of conformatlonally restricted peptide structures Is critical (, 2. Recently we have... 

We now turn to several examples where these techniques have been applied to peptide hormones, and show how we can study the conformational properties, including conformational minima and fluctuations, dynamics, and energetics of these molecules, and how these properties can in turn be used to design analogs. 

V. J. Hruby (1985). Design of peptide hormone and neurotransmitter analogs. Trends Pharmacol. Sci. 6 259-262. 

Howl, J., Langel, U., Hawtin, S. R., et al. (1997) Chimeric strategies for the rational design of bioactive analogs of small peptide hormones. FASEB J. 11, 582-590. 

Kourounakis Rekka ADVANCED DRUG DESIGN AND DEVELOPMENT Labaune HANDBOOK OF PHARMACOKINETICS The Toxicity Asssessment of Chemicals Macheras, Reppas Dressman BIOPHARMACEUTICS OF ORALLY ADMINISTERED DRUGS Martinez PEPTIDE HORMONES AS PROHORMONES Rainsford ANTI-RHEUMATIC DRUGS Actions and Side Effects... 

However, if the current attitudes persist and most scientists are not educated in the peptide sciences, and do not know how to design, synthesize, and evaluate peptides and peptidomimetics with desirable chemical and biological properties, the current ignorance and prejudice will become a self-fulfilling prophecy. Considering that Emil Fisher, perhaps the greatest organic chemist, was the father of peptide and protein chemistry, and that two peptide hormones, insulin and oxyto-... 

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