ABSTRACT
OBJECTIVE: Our aim was to define a repository of competences in Medicinal Chemistry, to be developed during Pharmacy studies and expected in professional practices, while highlighting the fundamental character of the subject and its interdisciplinary links within the Pharmaceutical Sciences. METHODS: A first version, based on both our professional and educational experience, consolidated by a review of educational articles and good practice guidelines, was obtained by following a competency-based approach. It was then completed by Medicinal Chemistry teachers in various French Pharmacy Faculties to obtain a comprehensive data set. The final version was reviewed in the light of relevant comments from 15 experts from related disciplines. RESULTS: A comprehensive competency framework with extensive practical applications was developed. CONCLUSIONS: This pilot study provides a teaching repository for medicinal chemistry for use by teachers of medicinal sciences. It highlights the fundamental role of the discipline within Pharmacy studies and provides links with professional practices. This repository will be useful to various teaching teams in a context of integrated disciplines and could be replicated in related disciplines.
Subject(s)
Education, Pharmacy , Pharmacy , Chemistry, Pharmaceutical , Curriculum , Pilot ProjectsABSTRACT
The selective deprotection of Lys(Mtt)-containing peptidyl resins was successfully monitored by RP-HPLC using very short linear gradients. RP-HPLC analyses of the acidic filtrates also revealed the partial cleavage of the Trt groups and of the peptide-resin bond. The absorbance of the Mtt carbocation at 470 nm is only twice that of the Trt cation. Thus, the UV monitoring at 470 nm seems to be inappropriate, especially at the end of the deprotection, when the Mtt and the Trt levels are comparable.
Subject(s)
Lysine/analogs & derivatives , Lysine/metabolism , Trityl Compounds/metabolism , Amino Acid Sequence , Chromatography, High Pressure Liquid , Gas Chromatography-Mass Spectrometry , Lysine/chemistry , Molecular Sequence Data , Peptides/chemical synthesis , Peptides/metabolism , Trityl Compounds/chemistry , Ultraviolet RaysABSTRACT
Solution-phase automated parallel synthesis of a Tic-based library is described. This library comprising 2560 members, was obtained from the combination of 80 carboxylic acids and 32 amines and was screened against Tc80 protease, a parasitic prolyl endopeptidase secreted by Trypanosoma cruzi. Pyrrolidine derivatives proved the most potent inhibitors with IC50 values found in the low nanomolar range.
