Chemical Synthesis and Analysis
Research Guide

Solid-phase peptide synthesis is a method for sequentially assembling peptides on a solid support, as first demonstrated by Merrifield (1963) in synthesizing a tetrapeptide. Amino acids are added one by one via amide bond formation, with side-chain protection and deprotection steps. This approach enables automated production of complex peptides for drug discovery.

Click chemistry refers to efficient, modular reactions like the copper(I)-catalyzed azide-alkyne cycloaddition, which regioselectively forms 1,2,3-triazoles in water, as described by Rostovtsev et al. (2002). Kolb et al. (2001) highlighted its preference for carbon-heteroatom bonds mimicking natural processes. It is applied in bioconjugation and peptidotriazole synthesis on solid phase by Tornøe et al. (2002).

Chemical ligation joins peptide fragments via chemoselective reactions, often using azide-alkyne cycloadditions for macrocycles and therapeutic peptides. Rostovtsev et al. (2002) detailed copper-catalyzed ligation of azides and terminal alkynes. This supports diversity-oriented synthesis in drug discovery targeting protein-protein interactions.

Base-specific chemical cleavages enable DNA sequencing by breaking labeled DNA at specific bases, as developed by Maxam and Gilbert (1980). Maxam and Gilbert (1977) described reactions cleaving preferentially at guanines, adenines, cytosines, and thymines. These methods identify base positions through fragment lengths.

Peptidotriazoles are synthesized on solid phase via copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides, reported by Tornøe et al. (2002). This regiospecific process works with primary, secondary, tertiary alkyl azides, and aryl azides. It provides a route to 1H-[1,2,3]-triazoles for drug-like molecules.