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Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety

1
Novo Nordisk Research Center, Indianapolis, IN 46241, USA
2
Department of Molecular, Developmental & Cell Biology, University of Colorado, Boulder, CO 80309, USA
3
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: Henry Mosberg, Tomi Sawyer and Carrie Haskell-Luevano
Molecules 2019, 24(10), 1855; https://doi.org/10.3390/molecules24101855
Received: 27 April 2019 / Revised: 10 May 2019 / Accepted: 12 May 2019 / Published: 14 May 2019
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Abstract

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. View Full-Text
Keywords: peptide; peptide-drug conjugate; mixed-mode pharmacology; GLP-1; GnRH; LHRH; chemical linker; cancer; diabetes; obesity; drug discovery peptide; peptide-drug conjugate; mixed-mode pharmacology; GLP-1; GnRH; LHRH; chemical linker; cancer; diabetes; obesity; drug discovery
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He, R.; Finan, B.; Mayer, J.P.; DiMarchi, R.D. Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety. Molecules 2019, 24, 1855.

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