Peptides, bonds synthetic

Several enzymes, none of which are completely specific for the enkephalins, are known to cleave Leu- and Met-enkephalin at various peptide bonds. The main enzymes that degrade enkephalin are 2inc metaHopeptidases. The first enkephalin-degrading enzyme to be identified, an aminopeptidase which cleaves the amino terminal Tyr-Gly bond (179), has been shown to be aminopeptidase-N (APN) (180). It is a cytoplasmic enzyme which is uniformly distributed throughout the brain. The increased analgesic activity of synthetic enkephalins substituted by D-amino acids at position 2, eg,... 

These oligomers for which synthetic routes have been developed, are formally obtained by either the introduction of a peptide bond isostere (e.g. y9-thiopeptides [263],... 

In view of these constraints, we recently suggested a different strategy for the improvement of the material properties of synthetic poly (amino acids) (12). Our approach is based on the replacement of the peptide bonds in the backbone of synthetic poly(amino acids) by a variety of "nonamide" Linkages. "Backbone modification," as opposed to "side chain modification," represents a fundamentally different approach that has not yet been explored in detail and that can potentially be used to prepare a whole family of structurally new polymers. 

The peptidyl transferase centre of the ribosome is located in the 50S subunit, in a protein-free environment (there is no protein within 15 A of the active site), supporting biochemical evidence that the ribosomal RNA, rather than the ribosomal proteins, plays a key role in the catalysis of peptide bond formation. This confirms that the ribosome is the largest known RNA catalyst (ribozyme) and, to date, the only one with synthetic activity. Adjacent to the peptidyl transferase centre is the entrance to the protein exit tunnel, through which the growing polypeptide chain moves out of the ribosome. 

Since then, catalytic antibodies which catalyze different chemical reactions have been described. The reactions range from ester or carbonate hydrolysis to carbon-carbon bond forming reactions, bimolecular amide formation or peptide bond cleavage, so the application of catalytic antibodies to general synthetic organic chemistry seems to be very promising [22]. 

Various EADIs have been synthesized using different synthetic routes [30-34], One of the widely used methods of preparation of E-alkene peptide bond isosteres involving ring opening of vinyl aziridines by cuprates has recently been reviewed [35,36],... 

There are many instances where a problem in protein chemistry or biology can be studied efficiently and effectively by semisynthesis. For this section, semisynthesis means the combination of a synthetic peptide with a large protein segment derived from natural sources. The combination can be by a covalent peptide bond or, in certain cases, by a specific... 

Corresponding improvements in the semisynthesis of proteins have been developed (see Section 5.1.11). They, too, have involved intermolecular and intramolecular reactions to form normal peptide bonds between small synthetic peptides and large protein components derived from natural sources or produced by recombinant techniques. In this case, there is the potential to produce derivatives of much larger proteins than can currently be prepared by total chemical synthesis. The total synthesis and semisynthesis approaches are useful for somewhat different purposes, but can be considered complementary together, they greatly broaden the field of protein chemistry and biology. 

Semisynthetic proteins can involve the combination of a synthetic with a biosynthetic portion by either noncovalent or covalent bonds. Among covalent bonds, there are available for use disulfide bonds, peptide bonds, and other, completely unnatural, bonds such as oximes and hydrazones. 

One enigmatic feature of renin is its extreme substrate specificity, its only known natural substrate being a single Leu-Val peptide bond of angiotensinogen. The minimal synthetic analog is the 6-13 octapeptide that encompasses the scissile peptide bond of angiotensinogen between residues 10 and 11 [5]. It has... 

From a strictly chemical point of view, the synthesis of glycosides still presents a formidable challenge to synthetic chemists in spite of major advances in the area [1], Unlike peptidic bonds, the formation of the glycosidic linkage is subject to various factors that include, among others, electronic, stereoelectronic, conformational, substituent, and reactivity effects generally associated with incipient oxocarbenium ions derived from carbohydrates. 

The commercial availability of protected /V-methyl amino acids [(Me)Xaa] of many proteinogenic amino acids (as well as other V-alkyl amino acids), the availability of procedures for the synthesis of protected V-alkyl analogues of all the protein amino acids, and the availability of synthetic procedures for site-selective alkylation during SPPS (see Section 10.1.2.1) allows the alkylation of nearly all peptide bonds in a given parent peptide. The synthesis of a series of V-alkyl peptide analogues based on the sequence of a given bioactive peptide (linear or cyclic) in which each peptide bond is successively alkylated and evaluation of the biological activity of this series will be called herein A-alkyl-scan (for example Me-scan, Et-scan, etc.)... 

Replacement of the peptide bond by a thioester group has been extensively applied in synthetic peptides used as enzyme substrates. Several classes of enzymes such as serine peptidases and metallo-endopeptidases are able to cleave efficiently thioester-modified amino acids and peptides. 61... 

The condensation reaction between two amino acid molecules, usually in the form of active esters, produces a dipeptide molecule (equation 16). The resulting amide bond (—CONH—) is often referred to as a peptide bond. This condensation reaction can be repeated to give a polypeptide chain (18). In naming the sequence of amino acid residues in the chain the customary habit of starting from the N-terminal (free amino) end will be adopted. Synthetic polypeptides made from a single amino acid type, i.e. R1 = R2 = R3 = = R" in (18), are known as homopolypeptides. Cyclic peptide molecules are also known and can occur naturally. 

The International Union of Biochemistry and Molecular Biology recommends that the term peptidase be used synonymously with the term peptide hydrolase (IUBMB, 1992). Thus, in this unit the term peptidase is used in reference to any enzyme that catalyzes the hydrolysis of peptide bonds, without distinguishing between exo- and endopeptidase activities. Peptidases may be assayed using native or modified proteins, peptides, or synthetic substrates. In this unit, the focus is on assays based on the hydrolysis of common, commercially available, protein substrates. Thus, the assays are not intended to be selective for a given peptidase they are designed to provide estimates of overall peptidase activity. Other units in this publication focus on synthetic or model substrates, which can be designed for the measurement of specific endo- and/or exopeptidase activities. 

Peptide bond formation using non-labile cobalt(III) complexes has now been developed to a useful synthetic level (Section 61.4.2.2.4), but few attempts have been made to use other metal centres. The formation of glycine peptide esters in the presence of copper(II) has been noted.133 Treatment of glycine esters with copper(II) (other metal ions can also be used) in a non-aqueous solvent at room temperature gave di-, tri- and tetra-glycine peptide esters. After carbobenzyloxyla-tion, the peptide esters were separated by column chromatography, and no evidence was obtained... 

Chloramphenicol. Chloramphenicol (Chloromycetin) is a synthetically produced agent that exerts antibacterial effects similar to those of erythromycin that is, it binds to the 50S subunit of bacterial ribosomes and inhibits peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic that is active against many gram-negative and gram-positive bacteria. This drug is administered systemically to treat serious infections such as typhoid fever, Haemophilus infections such as osteomyelitis, rickettsial infections such as Rocky Mountain spotted fever, and certain forms of meningitis. Chloramphenicol may also be administered topically to treat various skin, eye, and ear infections. 

---