An Alternative Solution for Peptide Drug Development

Michael Neely

doi:doi:10.11648/j.jddmc.20220804.11

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An Alternative Solution for Peptide Drug Development

Michael Neely

Published in Journal of Drug Design and Medicinal Chemistry (Volume 8, Issue 4)

Received: 4 October 2022 Accepted: 21 October 2022 Published: 28 October 2022

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Abstract

Polypeptide molecules are now a significant source of new chemical entities in the pharmaceutical industry. When exploring structure activity relationships of potential peptide sequences for various targeted receptors, medicinal chemists often encounter structures which have the desired affinity and specificity for the target, but which are intractable as potential drug molecules because of problems related to solubility or chemical stability. Significant cost and time are added to development cycles though the process of exploring alternative structures that will overcome such problems. A more expeditions approach to enabling a candidate molecule to be formulated as a drug would offer significant benefits in cost and time savings. Herein we introduce a novel concept for resolution of stability and solubility problems confronting formulators working with peptide drug molecules. Aprotic solvents such as Dimethyl Sulfoxide are shown to be safe and effective solvents for injectable peptide drugs, and are shown to offer long term shelf stability for such molecules in liquid formulations. The aprotic solvent technology obviates the need for costly and time consuming lyophilization processes. Its ability to increase solubility while obviating pH effects enables delivery of well tolerated small volume therapeutic doses. The technology also obviates the effect of pH and coupled with its ability to increase the concentration of peptide, affords a parenteral dose volume that is reduced and which spares the patient exposure to irritation that can be introduced by pH outside the range of neutrality.

Published in	Journal of Drug Design and Medicinal Chemistry (Volume 8, Issue 4)
DOI	10.11648/j.jddmc.20220804.11
Page(s)	46-49
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Peptides, Drug Formulation, Aprotic Solvents, Dimethylsulfoxide

References

[1]	Merrifield, R. B. (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. Journal of the American Chemical Society, 85, 2149-2154. doi: 10.1021/ja00897a025.
[2]	Wang et. al. Therapeutic peptides: current applications and future directions Nature, Sig Transduct Target Ther 7, 48 (2022).
[3]	Zapadka, et. al. Factors affecting the physical stability of peptide therapeutics, Royal Society Publishing October, 2017 https://doi.org/10.1098/rsfs.2017.0030
[4]	US Patent 5686411 Amylin agonist peptides and uses therefor 1997-11-11 Gaeta et al. 514/12.
[5]	Arvinte T, Cudd A, Drake AF. The structure and mechanism of formation of human calcitonin fibrils. J Biol Chem. 1993 Mar 25; 268 (9): 6415-22. PMID: 8454614.
[6]	Newswanger, et. al. J Diabetes Sci Technol. 2015 Jan; 9 (1): 24–33. Published online 2015 Jan 1. doi: 10.1177/1932296814565131.
[7]	US Patent 10987399, Stable formulations for parenteral injection of peptide drugs.
[8]	Xeris Pharmaceuticals, Inc. Chicago, IL The United States.
[9]	US Patent 11446310, Stable formulations for parenteral injection of small molecule drugs.
[10]	Website: https://www.globaldata.com/media/pharma/insulin-pramlintide-coformulations-disrupt-current-insulin-standards-says-globaldata/

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APA Style

Michael Neely. (2022). An Alternative Solution for Peptide Drug Development. Journal of Drug Design and Medicinal Chemistry, 8(4), 46-49. https://doi.org/10.11648/j.jddmc.20220804.11

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ACS Style

Michael Neely. An Alternative Solution for Peptide Drug Development. J. Drug Des. Med. Chem. 2022, 8(4), 46-49. doi: 10.11648/j.jddmc.20220804.11

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AMA Style

Michael Neely. An Alternative Solution for Peptide Drug Development. J Drug Des Med Chem. 2022;8(4):46-49. doi: 10.11648/j.jddmc.20220804.11

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@article{10.11648/j.jddmc.20220804.11,
  author = {Michael Neely},
  title = {An Alternative Solution for Peptide Drug Development},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {8},
  number = {4},
  pages = {46-49},
  doi = {10.11648/j.jddmc.20220804.11},
  url = {https://doi.org/10.11648/j.jddmc.20220804.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20220804.11},
  abstract = {Polypeptide molecules are now a significant source of new chemical entities in the pharmaceutical industry. When exploring structure activity relationships of potential peptide sequences for various targeted receptors, medicinal chemists often encounter structures which have the desired affinity and specificity for the target, but which are intractable as potential drug molecules because of problems related to solubility or chemical stability. Significant cost and time are added to development cycles though the process of exploring alternative structures that will overcome such problems. A more expeditions approach to enabling a candidate molecule to be formulated as a drug would offer significant benefits in cost and time savings. Herein we introduce a novel concept for resolution of stability and solubility problems confronting formulators working with peptide drug molecules. Aprotic solvents such as Dimethyl Sulfoxide are shown to be safe and effective solvents for injectable peptide drugs, and are shown to offer long term shelf stability for such molecules in liquid formulations. The aprotic solvent technology obviates the need for costly and time consuming lyophilization processes. Its ability to increase solubility while obviating pH effects enables delivery of well tolerated small volume therapeutic doses. The technology also obviates the effect of pH and coupled with its ability to increase the concentration of peptide, affords a parenteral dose volume that is reduced and which spares the patient exposure to irritation that can be introduced by pH outside the range of neutrality.},
 year = {2022}
}

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TY  - JOUR
T1  - An Alternative Solution for Peptide Drug Development
AU  - Michael Neely
Y1  - 2022/10/28
PY  - 2022
N1  - https://doi.org/10.11648/j.jddmc.20220804.11
DO  - 10.11648/j.jddmc.20220804.11
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 46
EP  - 49
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20220804.11
AB  - Polypeptide molecules are now a significant source of new chemical entities in the pharmaceutical industry. When exploring structure activity relationships of potential peptide sequences for various targeted receptors, medicinal chemists often encounter structures which have the desired affinity and specificity for the target, but which are intractable as potential drug molecules because of problems related to solubility or chemical stability. Significant cost and time are added to development cycles though the process of exploring alternative structures that will overcome such problems. A more expeditions approach to enabling a candidate molecule to be formulated as a drug would offer significant benefits in cost and time savings. Herein we introduce a novel concept for resolution of stability and solubility problems confronting formulators working with peptide drug molecules. Aprotic solvents such as Dimethyl Sulfoxide are shown to be safe and effective solvents for injectable peptide drugs, and are shown to offer long term shelf stability for such molecules in liquid formulations. The aprotic solvent technology obviates the need for costly and time consuming lyophilization processes. Its ability to increase solubility while obviating pH effects enables delivery of well tolerated small volume therapeutic doses. The technology also obviates the effect of pH and coupled with its ability to increase the concentration of peptide, affords a parenteral dose volume that is reduced and which spares the patient exposure to irritation that can be introduced by pH outside the range of neutrality.
VL  - 8
IS  - 4
ER  -

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Author Information

Michael Neely

Xeris Biopharma Holdings, Inc., St. Louis (MO), The United States

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Plain Text BibTeX RIS

APA Style

Michael Neely. (2022). An Alternative Solution for Peptide Drug Development. Journal of Drug Design and Medicinal Chemistry, 8(4), 46-49. https://doi.org/10.11648/j.jddmc.20220804.11

Copy | Download

ACS Style

Michael Neely. An Alternative Solution for Peptide Drug Development. J. Drug Des. Med. Chem. 2022, 8(4), 46-49. doi: 10.11648/j.jddmc.20220804.11

Copy | Download

AMA Style

Michael Neely. An Alternative Solution for Peptide Drug Development. J Drug Des Med Chem. 2022;8(4):46-49. doi: 10.11648/j.jddmc.20220804.11

Copy | Download

@article{10.11648/j.jddmc.20220804.11,
  author = {Michael Neely},
  title = {An Alternative Solution for Peptide Drug Development},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {8},
  number = {4},
  pages = {46-49},
  doi = {10.11648/j.jddmc.20220804.11},
  url = {https://doi.org/10.11648/j.jddmc.20220804.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20220804.11},
  abstract = {Polypeptide molecules are now a significant source of new chemical entities in the pharmaceutical industry. When exploring structure activity relationships of potential peptide sequences for various targeted receptors, medicinal chemists often encounter structures which have the desired affinity and specificity for the target, but which are intractable as potential drug molecules because of problems related to solubility or chemical stability. Significant cost and time are added to development cycles though the process of exploring alternative structures that will overcome such problems. A more expeditions approach to enabling a candidate molecule to be formulated as a drug would offer significant benefits in cost and time savings. Herein we introduce a novel concept for resolution of stability and solubility problems confronting formulators working with peptide drug molecules. Aprotic solvents such as Dimethyl Sulfoxide are shown to be safe and effective solvents for injectable peptide drugs, and are shown to offer long term shelf stability for such molecules in liquid formulations. The aprotic solvent technology obviates the need for costly and time consuming lyophilization processes. Its ability to increase solubility while obviating pH effects enables delivery of well tolerated small volume therapeutic doses. The technology also obviates the effect of pH and coupled with its ability to increase the concentration of peptide, affords a parenteral dose volume that is reduced and which spares the patient exposure to irritation that can be introduced by pH outside the range of neutrality.},
 year = {2022}
}

Copy | Download

TY  - JOUR
T1  - An Alternative Solution for Peptide Drug Development
AU  - Michael Neely
Y1  - 2022/10/28
PY  - 2022
N1  - https://doi.org/10.11648/j.jddmc.20220804.11
DO  - 10.11648/j.jddmc.20220804.11
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 46
EP  - 49
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20220804.11
AB  - Polypeptide molecules are now a significant source of new chemical entities in the pharmaceutical industry. When exploring structure activity relationships of potential peptide sequences for various targeted receptors, medicinal chemists often encounter structures which have the desired affinity and specificity for the target, but which are intractable as potential drug molecules because of problems related to solubility or chemical stability. Significant cost and time are added to development cycles though the process of exploring alternative structures that will overcome such problems. A more expeditions approach to enabling a candidate molecule to be formulated as a drug would offer significant benefits in cost and time savings. Herein we introduce a novel concept for resolution of stability and solubility problems confronting formulators working with peptide drug molecules. Aprotic solvents such as Dimethyl Sulfoxide are shown to be safe and effective solvents for injectable peptide drugs, and are shown to offer long term shelf stability for such molecules in liquid formulations. The aprotic solvent technology obviates the need for costly and time consuming lyophilization processes. Its ability to increase solubility while obviating pH effects enables delivery of well tolerated small volume therapeutic doses. The technology also obviates the effect of pH and coupled with its ability to increase the concentration of peptide, affords a parenteral dose volume that is reduced and which spares the patient exposure to irritation that can be introduced by pH outside the range of neutrality.
VL  - 8
IS  - 4
ER  -

Copy | Download