Recent Advances in Medicinal Chemistry

Volume: 1

Indexed in: Book Citation Index, Science Edition; BIOSIS Previews, 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


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.


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.


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