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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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 |
work_keys_str_mv |
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