Applications and Modifications of 1,2,3,4-Tetrahydroisoquinoline-3-Carboxylic Acid (Tic) in Peptides and Peptidomimetics Design and Discovery

Yingjie      Zhang; Hao      Fang; Wenfang      Xu

Abstract

Tic, short for 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, is a kind of unnatural α-amino acids. Due to its distinct geometrical conformation and biological activity, the structure of Tic, regarded as the surrogate of proline and the rigid analogue of phenylalanine or tyrosine, has been introduced into many compounds, which target diverse enzymes or receptors. The most successful example is that substituting the Tic residue for the proline residue of enalapril led to an approved drug quinapril. In this review, we will summarize the applications and modifications of Tic in peptides and peptidomimetics design and discovery, and hope to spark medicinal researchers inspiration in the field of protein and peptide drug design and optimization.

Keywords: 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), opioid ligands, farnesyl transferase inhibitors, integrin antagonists, angiotensin-converting enzyme inhibitors, prolyl endopeptidases inhibitors, endogenous mammalian, opiod receptor antagonists, linker, anxiety, depression, schizophrenia, addiction, eating disorders, glycoprotein receptors, immunosupressant