Pharmacological Chaperones: Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases

Marino Convertino, Jhuma Das, Nikolay V. Dokholyan

Research output: Contribution to journalReview article

36 Citations (Scopus)

Abstract

Errors in protein folding may result in premature clearance of structurally aberrant proteins, or in the accumulation of toxic misfolded species or protein aggregates. These pathological events lead to a large range of conditions known as conformational diseases. Several research groups have presented possible therapeutic solutions for their treatment by developing novel compounds, known as pharmacological chaperones. These cell-permeable molecules selectively provide a molecular scaffold around which misfolded proteins can recover their native folding and, thus, their biological activities. Here, we review therapeutic strategies, clinical potentials, and cost-benefit impacts of several classes of pharmacological chaperones for the treatment of a series of conformational diseases.

Original languageEnglish (US)
Pages (from-to)1471-1489
Number of pages19
JournalACS chemical biology
Volume11
Issue number6
DOIs
StatePublished - Jun 17 2016

Fingerprint

Pharmacology
Protein folding
Poisons
Protein Folding
Bioactivity
Scaffolds
Cost-Benefit Analysis
Proteins
Molecules
Therapeutics
Research
Costs
Protein Aggregates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

Cite this

@article{d47987937edf43e6b7b6300b8f6c5d05,
title = "Pharmacological Chaperones: Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases",
abstract = "Errors in protein folding may result in premature clearance of structurally aberrant proteins, or in the accumulation of toxic misfolded species or protein aggregates. These pathological events lead to a large range of conditions known as conformational diseases. Several research groups have presented possible therapeutic solutions for their treatment by developing novel compounds, known as pharmacological chaperones. These cell-permeable molecules selectively provide a molecular scaffold around which misfolded proteins can recover their native folding and, thus, their biological activities. Here, we review therapeutic strategies, clinical potentials, and cost-benefit impacts of several classes of pharmacological chaperones for the treatment of a series of conformational diseases.",
author = "Marino Convertino and Jhuma Das and Dokholyan, {Nikolay V.}",
year = "2016",
month = "6",
day = "17",
doi = "10.1021/acschembio.6b00195",
language = "English (US)",
volume = "11",
pages = "1471--1489",
journal = "ACS Chemical Biology",
issn = "1554-8929",
publisher = "American Chemical Society",
number = "6",

}

Pharmacological Chaperones : Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases. / Convertino, Marino; Das, Jhuma; Dokholyan, Nikolay V.

In: ACS chemical biology, Vol. 11, No. 6, 17.06.2016, p. 1471-1489.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Pharmacological Chaperones

T2 - Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases

AU - Convertino, Marino

AU - Das, Jhuma

AU - Dokholyan, Nikolay V.

PY - 2016/6/17

Y1 - 2016/6/17

N2 - Errors in protein folding may result in premature clearance of structurally aberrant proteins, or in the accumulation of toxic misfolded species or protein aggregates. These pathological events lead to a large range of conditions known as conformational diseases. Several research groups have presented possible therapeutic solutions for their treatment by developing novel compounds, known as pharmacological chaperones. These cell-permeable molecules selectively provide a molecular scaffold around which misfolded proteins can recover their native folding and, thus, their biological activities. Here, we review therapeutic strategies, clinical potentials, and cost-benefit impacts of several classes of pharmacological chaperones for the treatment of a series of conformational diseases.

AB - Errors in protein folding may result in premature clearance of structurally aberrant proteins, or in the accumulation of toxic misfolded species or protein aggregates. These pathological events lead to a large range of conditions known as conformational diseases. Several research groups have presented possible therapeutic solutions for their treatment by developing novel compounds, known as pharmacological chaperones. These cell-permeable molecules selectively provide a molecular scaffold around which misfolded proteins can recover their native folding and, thus, their biological activities. Here, we review therapeutic strategies, clinical potentials, and cost-benefit impacts of several classes of pharmacological chaperones for the treatment of a series of conformational diseases.

UR - http://www.scopus.com/inward/record.url?scp=84975516072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975516072&partnerID=8YFLogxK

U2 - 10.1021/acschembio.6b00195

DO - 10.1021/acschembio.6b00195

M3 - Review article

C2 - 27097127

AN - SCOPUS:84975516072

VL - 11

SP - 1471

EP - 1489

JO - ACS Chemical Biology

JF - ACS Chemical Biology

SN - 1554-8929

IS - 6

ER -