Some biologically active analogues of peptide hormones

5 Some biologically active analogues of peptide hormones 

Thionopeptides, with the —CSNH— group replacing one or more peptide bonds, closely resemble the related peptides. The —CSNH— group usually has trans substituents the major differences are the length of the C—N bond and the size of the sulphur atom. Thionopeptides are resistant to hydrolysis by proteinases. Despite 

Retropeptides contain the —NHCO— group and when the adjacent amino acids have the d configuration the structural resemblance to the related l peptide is quite close. Moreover, such retro-inverso peptides are stable to hydrolysis by pro-teinases. 

A third type of peptide analogue that has been studied widely is the azapeptide, in which the chiral carbon atom of an amino-acid residue is replaced by nitrogen. As with thionopeptides and retropeptides, azapeptides are resistant to the action of 

The enkephalins, H—Tyr—Gly—Gly—Phe—X—OH (X=Leu, Met), or so-called opioid peptides because they mimic the action of the opiates, morphine and heroin, have a very short half life in the body because all four peptide bonds are prone to undergoing proteolysis. The Tyr—Gly bond can be hydrolysed by amino-peptidases, the Gly—Gly bond by dipeptidylaminopeptidases, the Gly—Phe bond by enkephalinase and the Phe—Met and Phe—Leu bonds by carboxypeptidases. An enormous number of analogues have been synthesised, especially with the object of producing compounds that exert potent analgaesic action but are free from side effects. Protection of the susceptible bonds by changing the amino-acid sequence is the obvious way to achieve this. The analogue H—Tyr—d—Met—Gly—Phe— 

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