Recent Advances in Medicinal Chemistry

Volume: 1

Indexed in: EBSCO.

Recent advances in Medicinal Chemistry is a book series focused on leading-edge research on developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, ...
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Role of Intermediate States in Protein Folding and Misfolding

Pp. 433-455 (23)

Roberto Santucci, Fabio Polticelli, Federica Sinibaldi and Laura Fiorucci

Abstract

Most proteins fold into their native structure through defined pathways which involve a limited number of transient intermediates. Intermediates play a relevant role in the folding process; many diseases of genetic nature are in fact coupled with protein misfolding, which favours formation of stable inactive intermediate species of a protein. This review describes a number of diseases originated from protein misfolding and briefly discusses the mechanism(s) responsible, at molecular level, for these pathologies. It is also envisaged the native ⇄ molten globule transition since sometimes the conversion of the native form into a compact intermediate state permits a protein to carry out distinct physiological functions inside the cell. A non-native compact form of cyt c, for example, is involved in the programmed cell death (apoptosis) after that the protein is released from the mitochondrion; in addition, non-native forms of the protein are involved in some of the disorders attributed to amyloid formation.

Keywords:

Alzheimer’s disease, amyloid fibrils, apoptosis, conformational diseases, cystic fibrosis, cytochrome c, energy landscapes, folding pathways, intermediate states, Levinthal paradox, misfolding, molten globule, neurodegenerative diseases, phospholipids, protein folding.

Affiliation:

Department of Clinical Sciences and Translational Medicine, University of Rome ‘Tor Vergata’, Via Montpellier 1, 00133 Rome, Italy.