Peptide mimics

Several methods are being studied to enhance the stabiUty of peptide mimics and improve their stereochemical similarity to the endogenous peptides. For example, the tetrapeptide Cys—Val—Phe—Met, a potent inhibitor of Ras famesyltransferase, is proposed to exist in a turned conformation, which mimics the endogenous peptide during enzyme binding. This conformation is successhiUy mimicked by 3-amino-l-carboxymethyl-5-phenyl-benzodiazepin-2-onederivatives (198) (142). 

In an attempt to design the p-turn-peptide-mimics, aspartic acid (an amino acid also known as aspartate) and lysine (an amino acid especially found in gelatin and casein) were attached to each amine group of 1,3-diaminoada-mantane in the form of amide bonds. The term p-turn refers to a peptide chain that forms a tight loop such that the carbonyl oxygen of one residue is hydrogen... 

Temple, C. S., et al. Peptide mimics as substrates for the intestinal peptide transporter. J. Biol. Chem. 1998, 273, 20-22. 

Figure 7.2 Schematic showing the relationship of the native antigen to the peptide mimic. The native antigen (a protein) is shown as a winding, twisted line, so as to represent a hypothetical three-dimensional structure. The peptide represents the antibody-binding epitope (shown in dotted lines) of the native antigen. The epitope can represent a linear sequence of the native protein. Alternatively, the epitope can be formed by amino acids that are not immediately adjacent to each other in the primary sequence but brought together by the three-dimensional folding of the protein. Adapted with permission from Sompuram et al.6...

Both proteinaceous and non-proteinaceous analogs have been studied. Examples include a synthetic 20 amino acid adhesin peptide sequence copied from S. mutans and LTA of groups A and B streptococci. The synthetic peptide mimics a S. mutans adhesin that binds a salivary protein on dental surfaces and was shovm to inhibit bacterial adherence to immobilized salivary receptors in vitro. In vivo, this peptide hindered the recolonization by S. mutans on teeth that had been cleared of the... 

Peptide Mimics for Mannose-Recognizing Proteins -Interactions with Different Receptors... 

An interesting approach to the treatment of autoimmune diseases is design of peptide mimics that bind into the antigen-binding groove of specific MHC proteins. For example, a protease-resistant pyrrolinone-peptide hybrid has been designed to bind to the rheumatoid-arthritis-associated HLA-DR1.326... 

Incorporation of i,2, 6 -Trimcthyltyrosine into Bioactive Peptides Used in De Novo Design of Peptidomimetics and Nonpeptide Agonist Peptide Mimics... 

Several methods are being studied to enhance the stability of peptide mimics and improve their stereochemical similarity to the endogenous peptides. 

One may also favor models with spread-out features over models with features clustered on a specific part of the ligands. This may occur when the input molecules are large and feature rich, such as peptides and peptide mimics. 

Enzymes in the cross-linked crystal form are essentially impervious to degradation by exogenous proteases and from autolysis, in the case of CLCs of proteases themselves [5], This stability makes the enzyme-catalyzed preparation of peptides and peptide mimics truly practical [6], Examples will be discussed in more detail in Sec. IV. Further, one could conceive of using multiple enzymes in one-pot reaction systems mimicking natural biosynthetic cascades. Indeed, the application of this concept has been reported for a mixture of lipoamide dehydrogenase and lactate dehydrogenase [19],... 

Rittschof, D., Body odors and neutral-basic peptide mimics a review of responses by marine organisms, Am. Zool., 33, 487, 1993. 

Discussion Catalyst 38 serves as a peptide mimic of enzymes used for hydrocya-nations of aldehydes to provide access to a range of cyanohydrins in high yields and moderate to high enantioselectivities. Catalyst 38 was prepared in four steps from (benzyloxycarbonyl)-(S)-phenylalanine in good overall yield [58]. Hydrogen cyanide was produced according to literature precedent, via addition of an aqueous solution of sodium cyanide dropwise into dilute sulfuric acid and was stored in a freezer [61]. 

Boronates have been used in a variety of linker types either as linkers for diols [42] or as precursors for metal-mediated cleavage. A boronic acid ester, which contains an aryl iodide moiety attached by an appropriate tether, can act as an intramolecular arylation agent. A polymer-bound precursor furnished a macrocydic constrained / -tum peptide mimic via biaryl coupling, leading to cleavage [43] (Scheme 6.1.10). 

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