Peptidomimetic compounds

The D(R) isomer of the amino acid A-methyl-D-aspartate, more commonly known as NMDA serves as the endogenous agonist at a number of central nervous system (CNS) receptor sites. This agent is not only involved in neurotransmission, but also modulates responses elicited by other neurochemicals. A relatively simple peptide-like molecule has been found to act as an antagonist at NMDA receptors. This activity is manifested in vivo as antiepdeptic activity. This agent in addition blocks the nerve pain suffered by many diabetics, which is often called neuropathic pain. The synthesis begins by protecting the unnatural D-serine 

H2N C02H C6H5CH2OCOCI CbzHN, C02H CH3I CbzHN COaH 

A relatively simple derivative of phenylalanine shows hypoglycemic activity. This compound, nateglinide, is usually prescribed for use as an adjunct to either metformin, or one of the thiazolidine hypoglycemic agents. Catalytic reduction of the benzoic acid (85) leads to the corresponding substituted cyclohexane as a mixture of isomers. This compound is then esterified with methanol to give the methyl esters (86). Treatment with sodium hydride leads 86 to equilibrate to the more stable trans isomer 87 via its enolate. Condensation of 87 with the ester of phenylalanine (88) yields nateglinide (89) after saponifications.  

The hypoglycemic agent repaglinide may loosely be classed as a peptid-omimetic agent, because it essentially shows the same activity as nateglinide. The actual synthetic route is difficult to decipher from the patent in which it 

The synthesis of these agents begins with the hydrogenation of phenyl-glycine t-BOC amide (94) to the corresponding cyclohexyl derivative 95. The free carboxyl group is then coupled with the azetidine (96) to afford 

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Direct thrombin inhibitors such as hirudin, Hirulog, the peptide aldehyde efegatran, and peptidomimetic compound argatroban have undergone clinical trials. Their application in the prevention and treatment of deep vein thrombosis contin-... 

This macrocyclic peptidomimetic compound exhibits potent inhibitory activity against Escherichia coli deformylase as well as strong antibacterial activity against both Gram-positive and Gram-negative bacteria. 

SH2 domain-targeted peptidomimetic compounds [112] and displayed affinities comparable to those of F2Pmp-, or pTyr-containing analogues. 

Morphine as a peptidomimetic, PEPTIDOMIMETIC COMPOUND MOSSBAUER SPECTROSCOPY mRNA (GUANINE-7-)-METHYLTRANS-FERASE... 

PEPTIDOMIMETIC COMPOUND PEPTIDE METHIONINE SULFOXIDE REDUCTASE... 

PEPTIDOMIMETIC COMPOUND PEPTIDYL-ASPARTATE ENDOPEPTIDASE Peptidylglycine,... 

Nisin, because of its continued use as a preservative for more than 30 years 661 became an obvious target for a total synthesis 13 To date, it remains the only naturally occurring lanthionine peptide for which this feat has been achieved. In contrast to the lanthionine peptide syntheses of most other approaches already discussed, the total synthesis of nisin is based on a solution-synthesis strategy. Whilst, the total synthesis of the pentacyclic, 34-residue peptide nisin also demonstrated that such syntheses are not a commercially viable option for large amounts of lantibiotics, they have opened the way to useful synthetic methods for the synthesis of novel conformationally constrained peptides and peptidomimetic compounds. 

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