Peptide extended

In the first step of the peptidyl transferase reaction, a peptidyl tRNA molecule is bound in the P-site with its nascent peptide extending down the peptide exit tunnel (Fig. 4.1). An elongation factor binds to a factor binding site (FBS) and positions an aminoacyl-tRNA in the A-site. The a amino group of the aminoacyl-tRNA nucleophilically attacks the ester bond which connects the peptide to the tRNA bound in the P-site (Fig. 4.2). The ester bond is broken as an amide bond forms, and the peptide becomes one amino acid longer, and is now attached to the tRNA that in the A-site. Translocation of the products follows peptide bond formation, as the newly formed deacylated- tRNA of the P-site moves into the E-site, and as the newly elongated peptidyl-tRNA moves from the A-site into the P-site. 

Fmoc amino add (2 equiv), HATU (2 equiv), and DIPEA (4 equiv) were stirred at r.t. for 10 min. For Asn and Gin couplings, HOAt (2 equiv) as an auxiliary nucleophile is added. Using this protocol ACP (65-74) has been obtained with a purity of %%. For most complex peptides, extended coupling times and extra equivalents of reagents may be advisable. 

To some extent, the structures discussed above resemble turn structures in peptides. A typical peptide turn structure is depicted in Scheme 5.5. Ring constraints by hydrogen bonds define y-turns (7-membered ring) or p-tums (10-membered ring), whereas 13-membered rings are present in a-helices. Before and after the turn, the peptide extends as anti-parallel strands, often in p-sheets... 

Memfield s concept of a solid phase method for peptide synthesis and his devel opment of methods for carrying it out set the stage for an entirely new way to do chem ical reactions Solid phase synthesis has been extended to include numerous other classes of compounds and has helped spawn a whole new field called combinatorial chemistry Combinatorial synthesis allows a chemist using solid phase techniques to prepare hun dreds of related compounds (called libraries) at a time It is one of the most active areas of organic synthesis especially m the pharmaceutical industry... 

The techniques described thus far cope well with samples up to 10 kDa. Molecular mass determinations on peptides can be used to identify modifications occurring after the protein has been assembled according to its DNA code (post-translation), to map a protein structure, or simply to confirm the composition of a peptide. For samples with molecular masses in excess of 10 kDa, the sensitivity of FAB is quite low, and such analyses are far from routine. Two new developments have extended the scope of mass spectrometry even further to the analysis of peptides and proteins of high mass. 

Biosynthesis. Three separate genes encode the opioid peptides (see Fig. 1). Enkephalin is derived from preproenkephalin A, which contains six copies of Met-enkephalin and extended peptides, and one copy of Leu-enkephalin (62—66). ( -Endorphin is one of the many products of POMC, and represents the N-terminal 31 amino acids of P-Hpotropin (67,68). Three different dynorphin peptides are derived from the third opioid gene, preproenkephalin B, or preprodynorphin (69). The dynorphin peptides include dynorphin A, dynorphin B, and a-neo-endorphin. 

Group II consists of the enkephalins which come from the 267-aniino acid piecuisoi pro-enkephalin A [88402-54-4] (Fig. 2). This proteia contains four copies of Met-enkephalin, one copy of Leu-enkephalin, and the extended peptides Met-enkephalin-Arg -Phe (the last Met-enkephalin sequence ia Fig. 2) and Met-enkephalin-Arg -Gly -Leu (the fourth Met-enkephalin sequence ia Fig. 2) (25,26). AH of these products ate formed by trypsin-like cleavage between pairs of basic residues. The extended enkephalin peptides are further cleaved by carboxypeptidase E (27) to form authentic Met-enkephalin. 

Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

Elber et al. [48] applied this method to explore the dynamics of the C-peptide in water with impressive results. More than 30 trajectories of C-peptide were generated, and the process of helix fonnation in water was examined. Remarkably, a time step of 500 ps was used, which allowed for the study of peptide folding on extended time scales. 

Figure 13.29 Schematic diagram of the ptoline-tich region of Nef bound to an SH3 domain. The peptide region (red) binds in a groove that extends across the surface of SH3 (green). (Adapted from W. him, Structure 4 6S7-6S9, 1996.)...

Pleated p sheet (Section 27.19) Type of protein secondary structure characterized by hydrogen bonds between NH and C=0 groups of adjacent parallel peptide chains. The individual chains are in an extended zigzag conformation. 

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