Synthesis and nmr conformational studies of polyoxyethylene‐bound, α‐deuterated glutamate oligopeptides

Abstract

SynopsisThe syntheses of three series of glutamate oligopeptides attached to a macromolecular solubilizing polyoxyethylene (POE) group Boc-[Glu(OMe)],-OPOE, Ac-[Glu(OMe)],-OPOE, pGlu-[Gl~(0Me)]~~,-0POE ( n = 1-7) and their various analogs specifically deuterated a t individual a-CH positions using the liquid-phase method of peptide synthesis are described. It was shown that stepwise synthesis using the symmetrical anhydride gave homo-oligopeptides that are analytically pure. Fragment condensation methods using DCC-HOBt yield POE-peptides with POE-HOBt impurities but the peptide synthesis may be carried stoichiometrically with smaller quantities of amino acid derivatives. 360 MHz H-nmr conformational studies of these homo-oligopeptides in DMSO-4 are presented. The adeuterated peptides are shown to allow unequivocal homoligopeptide backbone NH assignments.

Organic Synthesis on Soluble Polymer Supports: Liquid-Phase Methodologies

“…Not hindered by the heterogeneity intrinsic to solid-phase systems, liquid-phase synthesis permits product characterization on soluble polymer supports by routine analytical methods. UV−visible, IR, and NMR spectroscopies and even TLC may be used to monitor reactions without requiring preliminary cleavage from the polymer support. ,, Reaction monitoring, purity assessment, and conformational studies of peptides were performed using 1 H NMR or 13 C NMR spectroscopy. , Moreover, aliquots taken for characterization may be returned to the reaction flask upon recovery from these nondestructive analytical methods. Chemical methods such as titration and derivatization can be routinely performed and allow subsequent characterization in the presence of the bound soluble support.…”

“…Analytically pure oligopeptides of glutamate and deuterated analogs were prepared on PEG 5000 up to the heptapeptide . Coupling reactions required 10−50% DMF in CH 2 Cl 2 to solubilize longer chain length peptides, and purity at each step after ether precipitation was assessed by 1 H NMR.…”

The profits and perils of international outsourcing

“…Rather, it is due to cost shifting and associated cost reduction. The following list identifies some of the more common and uncommon activities that highlight service diversity currently performed in India (Engardio et al, 2003;Ribeiro, 2002;Scott, 2003 • Wipro Spectramind Ltd. in New Delhi has branched out to process insurance claims for a major U.S. insurance company, provide help-desk support for a major U.S. Internet service provider, and employ seven Ph.D.'s in molecular biology to sift through scientific research data for Western pharmaceutical companies.…”

Novel Globular Polymeric Supports for Membrane-Enhanced Peptide Synthesis

“…OSN-assisted LPPS has been reported only by Livingston et al ,, for the synthesis of 1–5-mer model peptides at laboratory scale, using PEG linear polymers as support and ceramic membranes to purify the intermediate products after each step. However, linear polymers, which have also been used in several examples of LPPS ,,− ,,− have a limited application in MEPS . In this regard, the morphological characteristics of linear polymers (i.e., flexible chains in random coil) result in a significant loss of polymer through membranes during OSN, regardless of polymer size …”