دورية أكاديمية
أعرض في EDS

High-throughput infrared spectroscopy for quantification of peptides in drug discovery.

التفاصيل البيبلوغرافية
العنوان: High-throughput infrared spectroscopy for quantification of peptides in drug discovery.
المؤلفون: Hendrick N; Department of Chemistry, Boston University, Boston, MA, USA., Fraser D; Department of Chemistry, Boston University, Boston, MA, USA., Bennett R; Merck & Co. Inc., MRL, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Corazzata K; Department of Chemistry, Boston University, Boston, MA, USA., Adpressa DA; Merck & Co. Inc., MRL, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Makarov AA; Merck & Co. Inc., MRL, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: alexey.makarov@merck.com., Beeler A; Department of Chemistry, Boston University, Boston, MA, USA. Electronic address: beelera@bu.edu.
المصدر: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2023 May 30; Vol. 229, pp. 115350. Date of Electronic Publication: 2023 Mar 21.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: England NLM ID: 8309336 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-264X (Electronic) Linking ISSN: 07317085 NLM ISO Abbreviation: J Pharm Biomed Anal Subsets: MEDLINE
أسماء مطبوعة: Publication: <2006->: London : Elsevier Science
Original Publication: Oxford ; New York : Pergamon Press, c1983-
مواضيع طبية MeSH: Peptides*/chemistry , Drug Discovery*, Spectrophotometry, Infrared ; Solvents/chemistry ; Water
مستخلص: Peptides have gained an increasing importance in drug discovery as potential therapeutics. Discovery efforts toward finding new, efficacious peptide-based therapeutics have increased the throughput of peptide development, allowing the rapid generation of unique and pure peptide samples. However, high-throughput analysis of peptides may be still challenging and can encumber a high-throughput drug discovery campaign. We report herein a fit-for-purpose method to quantify peptide concentrations using high-throughput infrared spectroscopy (HT-IR). Through the development of this method, multiple critical method parameters were optimized including solvent composition, droplet deposition size, plate drying procedures, sample concentration, and internal standard. The relative absorbance of the amide region (1600-1750 cm -1 ) to the internal standard, K 3 Fe(CN) 6 (2140 cm -1 ), was determined to be most effective at providing lowest interference for measuring peptide concentration. The best sample deposition was achieved by dissolving samples in a 50:50 v/v allyl alcohol/water mixture. The developed method was used on 96-well plates and analyzed at a rate of 22 min per plate. Calibration curves to measure sample concentration versus response relationship displayed sufficient linearity (R 2 > 0.95). The repeatability and scope of detection was demonstrated with eighteen peptide samples that were measured with most values below 20% relative standard deviation. The linear dynamic range of the method was determined to be between 1 and 5 mg/mL. This developed HT-IR methodology could be a useful tool in peptide drug candidate lead identification and optimization processes.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: High-throughput; IR plate reader; Infrared spectroscopy; Peptides
المشرفين على المادة: 0 (Peptides)
0 (Solvents)
059QF0KO0R (Water)
تواريخ الأحداث: Date Created: 20230331 Date Completed: 20230425 Latest Revision: 20230425
رمز التحديث: 20230425
DOI: 10.1016/j.jpba.2023.115350
PMID: 37001275
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-264X
DOI:10.1016/j.jpba.2023.115350