The present chapter deals with the recent developments in synthetic
methodology, process development, and techniques modifications employed in
peptides, and proteins synthesis as well as semi-synthesis through solution phase
synthesis (SPS), and primarily in the solid phase peptide synthesis (SPPS) method in a
variety of sequential, divergent, convergent, and ligation-based strategies. It also dwells
upon the physicochemical, stereo-electronic, structural/chemical, and reaction
medium's related factors affecting the synthesis, geometric outcomes, purification, and
yields of the intended product. The chapter provides recent insights into coupling
reagents, linker’s role, and associated feasibilities in handling, solubility issues, and inprocess
product’s aggregation during synthesis, purification as well as discusses
techniques to resolve these issues with pertinent examples on different sets of
‘difficult’ and long-chain peptides and on diversely-sourced proteins’ syntheses
employing various approaches of different kinds for prototypical developments in the
field of protein and peptide chemical synthesis.
Keywords: Chemical ligation, Chemical synthesis, Convergent and divergent
peptide synthesis, Coupling medium, Coupling reagents, Cysteine knot synthesis,
Epimerization, Fragment condensation, Functional protein bioconjugate, Inverse
synthesis, Linear and Cyclic peptides, Native chemical ligation, Peptide and
protein-based drugs, Polymer-assisted synthesis, Polypeptide, Protein
conjugation, Protein structural modifications, Racemization, Selenoproteins,
Semi-synthesis, Solid support, Solution and solid phase peptide synthesis (SPS &
SPPS), Staudinger ligation, Thiol capture, Thiol peptides, Trans-membrane
proteins.