Peptide Hormones Introduction

When faced with a set of flexible molecules with too large a number of variables, one must turn to chemical modification to reduce the number of variables to a managable set. In the case of peptide hormones, introduction of proline eliminates the torsional degree of freedom < > by introducing a cyclic constraint, but adds the necessity of considering both cis and trans isomers of the amide bond. Replacement of the a-proton of an amino acid by a methyl group has been shown to reduce the number of possible combinations of values for the <(> and i > torsional rotation to essentially two (25). Introduction of a cyclic constraint in a linear flexible molecule reduces the... 

The retro-peptide bond is a true isosteric peptide bond surrogate and as such may offer an important tool to study topics such as the functional role of the peptide backbone in peptide hormone-receptor interactions, and modulation of metabolic stability and bioavailability. Partially modified retro-inverso-peptides (PMRI-peptides) (e.g., 2-4, 7 Scheme 1) result from a retro-inverso transformation of one or several peptide bonds in an amino- and carboxy-free peptide (e.g., 5 Scheme 1). Evidently, partial or exhaustive retro-inverso transformations result in the introduction of two non-amino acid residues into the... 

The introduction of retro-, retro-inverso-, and PMRI-peptides with free and blocked C-and N-termini has been successful in numerous biological systems such as neurotransmitters, inhibitors of proteases and protein kinases, sweeteners, antimicrobial peptides, hormones, adhesion molecules, antigenic epitopes, immuno-modulators, and immunological probes. Table 1 provides an exhaustive list of retro-, retro-inverso-, PMRI-, and end-group-modified re/ro-mvmo-pseudopeptides derived from bioactive peptides. 

Introduction. This review is based on papers published in I966, and is necessaxily selective in order to keep it short. Some of the newly proposed synthetic procedures are interesting but need further development. Only passing mention will be given to much important work in the field of peptide hormones, since this is covered in the chapter on non-steroidal hormones. 

The new era in the development of peptide S3mthesis began with the so-called carbobenzoxy method of Bergmann-Zervas (2). Thirty five years after its introduction the carbobenzoxy method is still the method of choice, especially since Bergmann and Zervas (3) have adapted it to almost all the known amino acids and du Vigneaud ( ) to S-benzyl cysteine. These procedures made possible the sjmthesis (1) of thousands of peptides and of peptide hormones e.g. oxytocin (du Vigneaud), ACTH (Schwyzer), insulin (Katsoyannis, Zahn, Du). 

Peptides and proteins are not strictly new therapeutic agents, indeed hormones, serum proteins and enzymes have been used as drags ever since the commercial introduction of insulin in 1923. However, significant... 

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