Peptide segments synthesis

Hojo H, Aimoto S (1991) Polypeptide synthesis using the S-Alkyl thioester of a partially protected peptide segment. Synthesis of the DNA-binding domain of c-Myb protein (142-193)-NH2. Bull Chem Soc Jpn 64 111... 

Albericio F, Barany G. Hypersensitive acid-labile (HAL) tris(alkoxy)benzyl ester anchoring for solid-phase synthesis of protected peptide segments. Tetrahedron Lett 1991 32 1015-1018. 

LA Carpino, BJ Cohen, KE Stephens, SY Sadat-Aalaee, J-H Tien, DC Lakgridge. (9-Fluorenylmethyl)oxycarbonyl (Fmoc) amino acid chlorides. Synthesis, characterization, and application to the rapid synthesis of short peptide segments. J Org Chem 51, 3732, 1986... 

Nakagawa, ET Kaiser. Synthesis of protected peptide segments and their assembly on a polymer-bound oxime application to the synthesis of a peptide model for plasma apolipoprotein A-I. J Org Chem 48, 678, 1983. 

M Gain, P Lloyd-Williams, F Albericio, E Giralt. Convergent solid-phase peptide synthesis. 12. Chromatographic techniques for the purification of protected peptide segments. Int J Pept Prot Res 46, 119, 1995. 

The hydrophobic peptide segments of El and E2, which attach the spike protein to the lipid bilayer, can be localized on the polypeptide chains by a mapping procedure first used by Dintzis (1961) to show that the synthesis of polypeptide chains begins at the amino-terminal end. The hydrophobic stubs left in the viral membrane after protease treatment are found at the carboxyl-terminal ends of both the El and the E2 polypeptides (Garoff and Sdderlund, 1978). 

The oxime 71d has several advantages over other resins, since the protected peptide segment can be cleaved by aminolysis under conditions which do not affect benzyl ester protecting groups. Moreover, the whole procedure is compatible with the Boc group employed for a-amino protection. The synthesis of several peptides using 71d has been... 

Scheme 19 Segment Synthesis by Reaction of a Peptide Thioacid with a Bromoacetyl Peptidel1001...

The insolubility of peptides is not limited to the solution phase and can occur during peptide synthesis on the solid phase where it manifests itself as the difficult sequence problem. On-resin peptide aggregation and poor peptide segment solubility are due to the formation of (3-sheet-like structures. Difficult sequences contain predominantly hydrophobic residues that consistently show incomplete acylation and a characteristic shrinkage of the peptide-resin during synthesis.111 Reversible backbone protection was introduced into Fmoc/ tBu SPPS after the study of synthesis failure during the assembly of difficult sequences1121 and is now routinely used to circumvent synthesis failure in SPPS. 

Kent, S. (1999). Chemical protein synthesis by solid phase ligation of unprotected peptide segments. J. Am. Chem. Soc., 121, 8720-7. 

The 1,3,4-oxadiazole moiety, in analogy to the 1,2,4-oxadiazole discussed in Section 11.2.5.1, has been used extensively as an ester or amide bioisostere, but also has only recently been applied as an amide replacement in actual peptide segments.1104-1071 The synthesis of the peptide surrogate 1,3,4-oxadiazole derivative 60 is shown in Scheme 18.11021 The N-protected amino acid Boc-Ala-OH (56) was coupled with ethanol to form the ester 57 which was subsequently reacted with hydrazine to form the amino acid hydrazide 58.11(1X1 The hydrazide 58 was reacted with ethyl oxalyl chloride at — 30 °C to room temperature to provide the diacylhydrazide 59. This intermediate was subsequently dehydrated with thionyl chloride in refluxing toluene to form the desired 1,3,4-oxadiazole 60 in >95% ee. Although the overall yields are only moderate, the reported enantioselectivities of the final compounds are very good (Table 4).11021... 

Synthesis of unusual amino acids, peptidomimetics, synthetic enzymes, and new drugs containing (5-lactam rings as an integral part of their structure, has currently renewed interest worldwide in this four-membered heterocycle [52-54]. Furthermore, the appropriately substituted and configured(5-lactam frameworks now constitute effective tools for the incorporation of a wide variety of both (5- and a-amino acids in short peptide segments of various biologically active molecules. 

Convergent methods avoid the cumulative disaster of linear synthesis. Access to large peptides can be provided by use of medium-sized peptide segments, easily available by solid-phase synthesis. There are two distinct approaches. One involves the synthesis and puri-... 

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