Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety

Peptides constitute molecular diversity with unique molecular mechanisms of action that are proven indispensable in the management of many human diseases, but of only a mere fraction relative to more traditional small molecule-based medicines. The integration of these two therapeutic modalities offe...

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Main Authors: Rongjun He, Brian Finan, John P. Mayer, Richard D. DiMarchi
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/24/10/1855
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spelling doaj-34c4245cb1554c8fb0fc701ee5156dbc2020-11-24T21:30:09ZengMDPI AGMolecules1420-30492019-05-012410185510.3390/molecules24101855molecules24101855Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and SafetyRongjun He0Brian Finan1John P. Mayer2Richard D. DiMarchi3Novo Nordisk Research Center, Indianapolis, IN 46241, USANovo Nordisk Research Center, Indianapolis, IN 46241, USADepartment of Molecular, Developmental & Cell Biology, University of Colorado, Boulder, CO 80309, USANovo Nordisk Research Center, Indianapolis, IN 46241, USAPeptides constitute molecular diversity with unique molecular mechanisms of action that are proven indispensable in the management of many human diseases, but of only a mere fraction relative to more traditional small molecule-based medicines. The integration of these two therapeutic modalities offers the potential to enhance and broaden pharmacology while minimizing dose-dependent toxicology. This review summarizes numerous advances in drug design, synthesis and development that provide direction for next-generation research endeavors in this field. Medicinal studies in this area have largely focused upon the application of peptides to selectively enhance small molecule cytotoxicity to more effectively treat multiple oncologic diseases. To a lesser and steadily emerging extent peptides are being therapeutically employed to complement and diversify the pharmacology of small molecule drugs in diseases other than just cancer. No matter the disease, the purpose of the molecular integration remains constant and it is to achieve superior therapeutic outcomes with diminished adverse effects. We review linker technology and conjugation chemistries that have enabled integrated and targeted pharmacology with controlled release. Finally, we offer our perspective on opportunities and obstacles in the field.https://www.mdpi.com/1420-3049/24/10/1855peptidepeptide-drug conjugatemixed-mode pharmacologyGLP-1GnRHLHRHchemical linkercancerdiabetesobesitydrug discovery
collection DOAJ
language English
format Article
sources DOAJ
author Rongjun He
Brian Finan
John P. Mayer
Richard D. DiMarchi
spellingShingle Rongjun He
Brian Finan
John P. Mayer
Richard D. DiMarchi
Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety
Molecules
peptide
peptide-drug conjugate
mixed-mode pharmacology
GLP-1
GnRH
LHRH
chemical linker
cancer
diabetes
obesity
drug discovery
author_facet Rongjun He
Brian Finan
John P. Mayer
Richard D. DiMarchi
author_sort Rongjun He
title Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety
title_short Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety
title_full Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety
title_fullStr Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety
title_full_unstemmed Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety
title_sort peptide conjugates with small molecules designed to enhance efficacy and safety
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2019-05-01
description Peptides constitute molecular diversity with unique molecular mechanisms of action that are proven indispensable in the management of many human diseases, but of only a mere fraction relative to more traditional small molecule-based medicines. The integration of these two therapeutic modalities offers the potential to enhance and broaden pharmacology while minimizing dose-dependent toxicology. This review summarizes numerous advances in drug design, synthesis and development that provide direction for next-generation research endeavors in this field. Medicinal studies in this area have largely focused upon the application of peptides to selectively enhance small molecule cytotoxicity to more effectively treat multiple oncologic diseases. To a lesser and steadily emerging extent peptides are being therapeutically employed to complement and diversify the pharmacology of small molecule drugs in diseases other than just cancer. No matter the disease, the purpose of the molecular integration remains constant and it is to achieve superior therapeutic outcomes with diminished adverse effects. We review linker technology and conjugation chemistries that have enabled integrated and targeted pharmacology with controlled release. Finally, we offer our perspective on opportunities and obstacles in the field.
topic peptide
peptide-drug conjugate
mixed-mode pharmacology
GLP-1
GnRH
LHRH
chemical linker
cancer
diabetes
obesity
drug discovery
url https://www.mdpi.com/1420-3049/24/10/1855
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