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NMR processing:
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Side-chains:
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NOEs:
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UNIO Candid
ASDP
Structure from NMR restraints:
Ab initio:
GeNMR
Cyana
XPLOR-NIH
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Fragment-based:
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Template-based:
GeNMR
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Refinement:
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Structure from chemical shifts:
Fragment-based:
WeNMR CS-Rosetta
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Homology-based:
CS23D
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Torsion angles from chemical shifts:
Preditor
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Secondary structure from chemical shifts:
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Flexibility from chemical shifts:
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Interactions from chemical shifts:
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Chemical shifts re-referencing:
Shiftcor
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NMR model quality:
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NMR spectrum prediction:
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Flexibility from structure:
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Methyl S2
B-factor
Molecular dynamics:
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Chemical shifts prediction:
From structure:
Shiftx2
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ArShift- Aromatic
ShiftS
Proshift
PPM
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From sequence:
Shifty
Camcoil
Poulsen_rc_CS
Disordered proteins:
MAXOCC
Format conversion & validation:
CCPN
From NMR-STAR 3.1
Validate NMR-STAR 3.1
NMR sample preparation:
Protein disorder:
DisMeta
Protein solubility:
camLILA
ccSOL
Camfold
camGroEL
Zyggregator
Isotope labeling:
UPLABEL
Solid-state NMR:
sedNMR


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Old 06-19-2020, 03:16 PM
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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]



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