Biomedical subjects

Jordi Alsina

Publications and source records attributed to Jordi Alsina.

5 recordsLinked to original sources

PubMed2005

Backbone amide linker strategies for the solid-phase synthesis of C-terminal modified peptides.

This chapter describes backbone amide linker (BAL) strategies for the Nalpha-Fmoc solid-phase synthesis of C-terminal modified peptides. Most solid-phase protocols for the assembly of such peptides have limited generality, because they rely on the Calpha-carboxyl for attachment to the solid support. In the BAL approach, the growing peptide chain is anchored through a backbone nitrogen, thus allowing significant flexibility for chemical modification of the C-termini. In effect, any peptide containing C-terminal variations can be prepared in overall good purity and yield, with minimal side reactions, by using one or more of three variations (original and two modifications) of the BAL strategy.

Acylation↗

PubMed2004

Solid-phase synthesis of constrained terminal and internal lactam peptidomimetics.

Lactams are key components of many peptidomimetic structures. Five- and six-membered lactam peptidomimetics with hydrogen or amino acid side chains at the alpha-position can be constructed from peptide precursors during a solid-phase synthesis. There is no significant racemization of remote stereocenters during synthesis.

Cyclization↗

PubMed2003

Solid-phase synthesis of C-terminal modified peptides.

Solid-phase synthesis of biomolecules, of which peptides are the principal example, is well established. However, synthetic peptides containing modifications at the carboxy termini are often desired because of their potential therapeutic properties. As a result, there is a necessity for effective solid-phase strategies for the preparation of peptides with C-terminal end groups other than the usual carboxylic acid and carboxamide functionalities. The present article primarily reviews literature reports on methods for solid-phase synthesis of C-terminal modified peptides. In addition, general information about biological activities and/or synthetic applications of each individual class of peptide is also provided.

Alcohols↗

PubMed2002

A solid-phase synthetic route to unnatural amino acids with diverse side-chain substitutions.

Reacting imine derivatives of resin-bound amino acids with alpha,omega-dihaloalkanes provides highly versatile intermediates to racemic alpha,alpha-disubstituted amino acids with a wide variety of side-chain functionality. Two strategies were developed to convert the intermediate omega-chloro or omega-bromo derivatives to the desired products. Together, they allow the creation of amino acids with diverse functionalities (omega-chlorides, nitriles, azides, acetates, thioacetates, thioethers, secondary and tertiary aliphatic amines, and anilines) placed at varying chain lengths (2-5) from the alpha-center of the amino acid.

Alkylation↗

PubMed1999

Backbone Amide Linker (BAL) Strategy for N(alpha)()-9-Fluorenylmethoxycarbonyl (Fmoc) Solid-Phase Synthesis of Unprotected Peptide p-Nitroanilides and Thioesters(1).

A novel and general backbone amide linker (BAL) strategy has been devised for preparation of C-terminal modified peptides containing hindered, unreactive, and/or sensitive moieties, in concert with N(alpha)()-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis protocols. This strategy comprises (i) start of peptide synthesis by anchoring the penultimate residue, with its carboxyl group orthogonally protected, through the backbone nitrogen, (ii) continuation with standard protocols for peptide chain elongation in the C --> N direction, (iii) selective orthogonal removal of the carboxyl protecting group, (iv) solid-phase activation of the pendant carboxyl and coupling with the desired C-terminal residue, and (v) final cleavage/deprotection to release the free peptide product into solution. To illustrate this approach, several model peptide p-nitroanilides and thioesters have been prepared in excellent yields and purities, with minimal racemization. Such compounds are very difficult to prepare by standard Fmoc chemistry, including the BAL strategy as originally envisaged.

Journal Article↗