The Application of Microsampling Disks in Circular Dichroism Spectroscopy for Peptide and Nucleic Acid Drugs

In recent years, there has been a growing focus on the development of medium-sized drugs based on peptides or nucleic acids owing to their potential therapeutic benefits. As some of these medium-sized drugs exert their therapeutic effects by adopting specific secondary structures, evaluating their c...

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Published inChemical & pharmaceutical bulletin Vol. 72; no. 7; pp. 658 - 663
Main Authors Tsuji, Genichiro, Misawa, Takashi, Demizu, Yosuke
Format Journal Article
LanguageEnglish
Published Japan The Pharmaceutical Society of Japan 11.07.2024
Japan Science and Technology Agency
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Abstract In recent years, there has been a growing focus on the development of medium-sized drugs based on peptides or nucleic acids owing to their potential therapeutic benefits. As some of these medium-sized drugs exert their therapeutic effects by adopting specific secondary structures, evaluating their conformational states is crucial to ensure the efficacy, quality, and safety of the drug products. It is important to assess the structural integrity of biomolecular therapeutics to guarantee their intended pharmacological activity and maintain the required standards for drug development and manufacturing. One widely utilized technique for quality evaluation is secondary structural analysis using circular dichroism (CD) spectroscopy. Given the higher production and quality control costs associated with medium-sized drugs compared with small-molecule drugs, developing analytical techniques that enable CD analysis with reduced sample volumes is highly desirable. Herein, we focused on a microsampling disk-type cell as a potential solution for reducing the required sample volume. We investigated whether CD spectral analysis using a microsampling disk could provide equivalent spectra compared with the standard cell (sample volume: approx. 300 µL). Our findings demonstrated that the microsampling disk (sample volume: 2–10 µL) could be successfully applied to CD spectral analysis of peptide and nucleic acid drugs, paving the way for more efficient and cost-effective quality evaluation processes.
AbstractList In recent years, there has been a growing focus on the development of medium-sized drugs based on peptides or nucleic acids owing to their potential therapeutic benefits. As some of these medium-sized drugs exert their therapeutic effects by adopting specific secondary structures, evaluating their conformational states is crucial to ensure the efficacy, quality, and safety of the drug products. It is important to assess the structural integrity of biomolecular therapeutics to guarantee their intended pharmacological activity and maintain the required standards for drug development and manufacturing. One widely utilized technique for quality evaluation is secondary structural analysis using circular dichroism (CD) spectroscopy. Given the higher production and quality control costs associated with medium-sized drugs compared with small-molecule drugs, developing analytical techniques that enable CD analysis with reduced sample volumes is highly desirable. Herein, we focused on a microsampling disk-type cell as a potential solution for reducing the required sample volume. We investigated whether CD spectral analysis using a microsampling disk could provide equivalent spectra compared with the standard cell (sample volume: approx. 300 µL). Our findings demonstrated that the microsampling disk (sample volume: 2–10 µL) could be successfully applied to CD spectral analysis of peptide and nucleic acid drugs, paving the way for more efficient and cost-effective quality evaluation processes.
In recent years, there has been a growing focus on the development of medium-sized drugs based on peptides or nucleic acids owing to their potential therapeutic benefits. As some of these medium-sized drugs exert their therapeutic effects by adopting specific secondary structures, evaluating their conformational states is crucial to ensure the efficacy, quality, and safety of the drug products. It is important to assess the structural integrity of biomolecular therapeutics to guarantee their intended pharmacological activity and maintain the required standards for drug development and manufacturing. One widely utilized technique for quality evaluation is secondary structural analysis using circular dichroism (CD) spectroscopy. Given the higher production and quality control costs associated with medium-sized drugs compared with small-molecule drugs, developing analytical techniques that enable CD analysis with reduced sample volumes is highly desirable. Herein, we focused on a microsampling disk-type cell as a potential solution for reducing the required sample volume. We investigated whether CD spectral analysis using a microsampling disk could provide equivalent spectra compared with the standard cell (sample volume: approx. 300 µL). Our findings demonstrated that the microsampling disk (sample volume: 2-10 µL) could be successfully applied to CD spectral analysis of peptide and nucleic acid drugs, paving the way for more efficient and cost-effective quality evaluation processes.In recent years, there has been a growing focus on the development of medium-sized drugs based on peptides or nucleic acids owing to their potential therapeutic benefits. As some of these medium-sized drugs exert their therapeutic effects by adopting specific secondary structures, evaluating their conformational states is crucial to ensure the efficacy, quality, and safety of the drug products. It is important to assess the structural integrity of biomolecular therapeutics to guarantee their intended pharmacological activity and maintain the required standards for drug development and manufacturing. One widely utilized technique for quality evaluation is secondary structural analysis using circular dichroism (CD) spectroscopy. Given the higher production and quality control costs associated with medium-sized drugs compared with small-molecule drugs, developing analytical techniques that enable CD analysis with reduced sample volumes is highly desirable. Herein, we focused on a microsampling disk-type cell as a potential solution for reducing the required sample volume. We investigated whether CD spectral analysis using a microsampling disk could provide equivalent spectra compared with the standard cell (sample volume: approx. 300 µL). Our findings demonstrated that the microsampling disk (sample volume: 2-10 µL) could be successfully applied to CD spectral analysis of peptide and nucleic acid drugs, paving the way for more efficient and cost-effective quality evaluation processes.
ArticleNumber c24-00244
Author Misawa, Takashi
Demizu, Yosuke
Tsuji, Genichiro
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10.1016/j.addr.2023.114872
10.1016/S0014-4827(03)00257-X
10.1007/978-1-4939-9504-2_14
10.1007/978-1-4939-9504-2_11
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circular dichroism (CD) spectra
microsampling disk
peptide
nucleic acid
medium-sized drug
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– reference: 19) Scott L. J., Drugs, 80, 335–339 (2020).
– reference: 17) Hair P., Fiona Cameron F., McKeage K., Drugs, 73, 487–493 (2013).
– reference: 8) Kawamoto Y., Wu Y., Takahashi Y., Takakura Y., Adv. Drug Deliv. Rev., 199, 114872 (2023).
– reference: 1) Cheng J., Zhou J., Kong L., Wang H., Zhang Y., Wang X., Liu G., Chu Q., RSC Med. Chem., 14, 2496–2508 (2023).
– reference: 22) Migliore M., Bonvicini A., Tognetti V., Guilhaudis L., Baaden M., Oulyadi H., Joubert L., Ségalas-Milazzo I., Phys. Chem. Chem. Phys., 22, 1611–1623 (2020).
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– reference: 14) Wiśniewski K., Methods Mol. Biol., 2001, 235–271 (2019).
– reference: 20) Watanabe N., Nagata T., Satou Y., Masuda S., Saito T., Kitagawa H., Komaki H., Takagaki K., Takeda S., Mol. Ther. Nucleic Acids, 13, 442–449 (2018).
– reference: 7) Egli M., Manoharan M., Nucleic Acids Res., 51, 2529–2573 (2023).
– reference: 15) Lexchin J., Mintzes B., Drug Ther. Bull., 61, 182–188 (2023).
– reference: 23) Bishop G. R., Chaires J. B., Curr. Protoc. Nucleic Acid Chem., Chapter 7, 7.11.1–7.11.8 (2003).
– reference: 2) Nakamura Y., Biochimie, 145, 22–33 (2018).
– reference: 16) Weiss M. A., Vitam. Horm., 80, 33–49 (2009).
– reference: 9) Nornes S., Growth C., Camp E., Ey P., Lardelli M., Exp. Cell Res., 289, 124–132 (2003).
– reference: 21) “Supplement I to The Japanese Pharmacopoeia,” 18th edition, 2022.
– reference: 4) Tanada M., Tamiya M., Matsuo A., et al., J. Am. Chem. Soc., 145, 16610–16620 (2023).
– reference: 12) Kondo Y., Biophys. J., 104, 72a (2013).
– reference: 18) Food and Drug Administration. “Highlights of Prescribing Information (Macugen).” 3–12 (July 2007): ‹https://pi.bauschhealth.com/globalassets/BHC/PI/Macugen-PI.pdf?ver=2021-05-21-022911-740›, cited 16 April, 2024.
– reference: 5) Merz M. L., Habeshian S., Li B., David J. G. L., Nielsen A. L., Ji X., Il Khwildy K., Duany Benitez M. M., Phothirath P., Heinis C., Nat. Chem. Biol., 20, 624–633 (2024).
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– reference: 13) Wilson A. C., Meethal S. V., Bowen R. L., Atwood C. S., Expert Opin. Investig. Drugs, 16, 1851–1863 (2007).
– reference: 3) Tsiamantas C., Otero–Ramirez M. E., Suga H., Methods Mol. Biol., 2001, 299–315 (2019).
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– ident: 20
  doi: 10.1016/j.omtn.2018.09.017
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  doi: 10.1007/s40265-013-0042-2
– ident: 22
  doi: 10.1039/C9CP05776E
– ident: 2
  doi: 10.1016/j.biochi.2017.10.006
– ident: 7
  doi: 10.1093/nar/gkad067
– ident: 13
  doi: 10.1517/13543784.16.11.1851
– ident: 5
  doi: 10.1038/s41589-023-01496-y
– ident: 10
  doi: 10.1039/D1SC00165E
– ident: 11
– ident: 19
  doi: 10.1007/s40265-020-01269-0
– ident: 23
  doi: 10.1002/0471142700.nc0711s11
– ident: 16
– ident: 6
  doi: 10.1038/s41565-021-00898-0
– ident: 15
  doi: 10.1136/dtb.2023.000007
– ident: 1
  doi: 10.1039/D3MD00487B
– ident: 12
  doi: 10.1016/j.bpj.2012.11.437
– ident: 4
  doi: 10.1021/jacs.3c03886
– ident: 8
  doi: 10.1016/j.addr.2023.114872
– ident: 9
  doi: 10.1016/S0014-4827(03)00257-X
– ident: 3
  doi: 10.1007/978-1-4939-9504-2_14
– ident: 14
  doi: 10.1007/978-1-4939-9504-2_11
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SubjectTerms Circular Dichroism
circular dichroism (CD) spectra
Cost analysis
Dichroism
Drug development
Drugs
Effectiveness
medium-sized drug
microsampling disk
nucleic acid
Nucleic acids
Nucleic Acids - analysis
Nucleic Acids - chemistry
peptide
Peptides
Peptides - analysis
Peptides - chemistry
Product safety
Quality assessment
Quality control
secondary structure
Spectroscopic analysis
Spectroscopy
Spectrum analysis
Structural analysis
Structural integrity
Title The Application of Microsampling Disks in Circular Dichroism Spectroscopy for Peptide and Nucleic Acid Drugs
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