View Single Post
  #1  
Unread 06-19-2020, 03:16 PM
nmrlearner's Avatar
nmrlearner nmrlearner is offline
Senior Member
 
Join Date: Jan 2005
Posts: 23,135
Points: 193,617, Level: 100
Points: 193,617, Level: 100 Points: 193,617, Level: 100 Points: 193,617, Level: 100
Level up: 0%, 0 Points needed
Level up: 0% Level up: 0% Level up: 0%
Activity: 50.7%
Activity: 50.7% Activity: 50.7% Activity: 50.7%
Last Achievements
Award-Showcase
NMR Credits: 0
NMR Points: 0
Downloads: 0
Uploads: 0
Default Quality Control of Therapeutic Peptides by 1H NMR HiFSA Sequencing.

Quality Control of Therapeutic Peptides by 1H NMR HiFSA Sequencing.

Related Articles Quality Control of Therapeutic Peptides by 1H NMR HiFSA Sequencing.

J Org Chem. 2019 03 15;84(6):3055-3073

Authors: Choules MP, Bisson J, Gao W, Lankin DC, McAlpine JB, Niemitz M, Jaki BU, Franzblau SG, Pauli GF

Abstract
Ensuring identity, purity, and reproducibility are equally essential during synthetic chemistry, drug discovery, and for pharmaceutical product safety. Many peptidic APIs are large molecules that require considerable effort for integrity assurance. This study builds on quantum mechanical 1H iterative Full Spin Analysis (HiFSA) to establish NMR peptide sequencing methodology that overcomes the intrinsic limitations of principal compendial methods in identifying small structural changes or minor impurities that affect effectiveness and safety. HiFSA sequencing yields definitive identity and purity information concurrently, allowing for API quality assurance and control (QA/QC). Achieving full peptide analysis via NMR building blocks, the process lends itself to both research and commercial applications as 1D 1H NMR (HNMR) is the most sensitive and basic NMR experiment. The generated HiFSA profiles are independent of instrument or software tools and work at any magnetic field strength. Pairing with absolute or 100% qHNMR enables quantification of mixtures and/or determination of peptide conformer populations. Demonstration of the methodology uses single amino acids (AAs) and peptides of increasing size, including the octapeptide, angiotensin II, and the nonapeptide, oxytocin. The feasibility of HiFSA coupled with automated NMR and qHNMR for use in QC/QA efforts is established through case-based examples and recommended procedures.


PMID: 30793905 [PubMed - indexed for MEDLINE]



More...
Reply With Quote


Did you find this post helpful? Yes | No