piperidines and gamma-collidine

Solid-Phase Peptide Synthesis (SPPS) is a rapid and efficient methodology for the chemical synthesis of peptides and small proteins. However, the assembly of peptide sequences classified as "difficult" poses severe synthetic problems in SPPS for the occurrence of extensive aggregation of growing peptide chains which often leads to synthesis failure. In this framework, we have investigated the impact of different synthetic procedures on the yield and final purity of three well-known "difficult peptides" prepared using oxyma as additive for the coupling steps. In particular, we have comparatively investigated the use of piperidine and morpholine/DBU as deprotection reagents, the addition of DIPEA, collidine and N-methylmorpholine as bases to the coupling reagent. Moreover, the effect of different agitation modalities during the acylation reactions has been investigated. Data obtained represent a step forward in optimizing strategies for the synthesis of "difficult peptides".

Topics: Acylation; Amino Acid Sequence; Ethylamines; Morpholines; Peptides; Piperidines; Pregnadienes; Protein Aggregates; Pyridines; Solid-Phase Synthesis Techniques

Microchip capillary electrophoresis (CE), coupled with indirect fluorescence detection was investigated for estimating the pK(a) values of non-fluorescent compounds. The CE method is based on the differences in electrophoretic mobility of the analyte as a function of the pH of the running buffer. Nine compounds were tested, including several of pharmaceutical importance, with pK(a) values from 10.3 to 4.6. All buffers contained 5-TAMRA as the fluorescent probe for indirect detection. Calculated pK(a) values agreed well with literature values obtained by traditional methods, differing not more than 0.2 from the literature value. The current work on single lane chips demonstrates the principle of microchip CE with indirect detection as a viable method for estimating pK(a) values. However, increased throughput will be required using a multilane chip to enable the approach to be used practically.

Topics: Aniline Compounds; Chemical Phenomena; Chemistry, Physical; Cimetidine; Electrophoresis, Microchip; Ethosuximide; Fluorescence; Fluorescent Dyes; Hydrogen-Ion Concentration; Piperidines; Prilocaine; Procaine; Pyridines; Ranitidine; Reproducibility of Results; Rhodamines; Sulfanilamide; Sulfanilamides; Uracil