Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 36Chemical Synthesis and AnalysisAdvanced Drug Delivery SystemsDrug Solubulity and Delivery Systems

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

Improvement of enzymatic stability and intestinal permeability of deuterohemin-peptide conjugates by specific multi-site N-methylation

Dong, Qing-Guang, Zhang, Yong, Wang, Meng-Shu, Feng, Jiao, Zhang, Hai-Hong, Wu, Yong-Ge, Gu, Tie-Jun, Yu, Xiang-Hui, Jiang, Chun-Lai, Chen, Yan, Li, Wei, Kong, Wei·2012·Amino Acids
DOI 10.1007/s00726-012-1322-y
Open this paper in CoChat — free account

Abstract

The deuterohemin-peptide conjugate, DhHP-6 (Dh-β-AHTVEK-NH(2)), is a microperoxidase mimetic, which has demonstrated substantial benefits in vivo as a scavenger of reactive oxygen species (ROS). In this study, specific multi-site N-methylated derivatives of DhHP-6 were designed and synthesized to improve metabolic stability and intestinal absorption, which are important factors for oral delivery of therapeutic peptides and proteins. The DhHP-6 derivatives were tested for (1) scavenging potential of hydrogen peroxide (H(2)O(2)); (2) permeability across Caco-2 cell monolayers and everted gut sacs; and (3) enzymatic stability in serum and intestinal homogenate. The results indicated that the activities of the DhHP-6 derivatives were not influenced by N-methylation, and that tri-N-methylation of DhHP-6 could significantly increase intestinal flux, resulting in a two- to threefold higher apparent permeability coefficient. In addition, molecules with N-methylation at selected sites (e.g., Glu residue) showed high resistance against proteolytic degradation in both diluted serum and intestinal preparation, with 50- to 140-fold higher half-life values. These findings suggest that the DhHP-6 derivatives with appropriate N-methylation could retain activity levels equivalent to that of the parent peptide, while showing enhanced intestinal permeability and stability against enzymatic degradation. The tri-N-methylated peptide Dh-β-AH(Me)T(Me)V(Me)EK-NH(2) derived from this study may be developed as a promising candidate for oral administration.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00726-012-1322-y

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 3

  1. Lister-James J, Dean RT, Pearson DA, Wilson DM (2001) Novel somatostatin analogs. WO 01/44177 A2
  2. Liu, YL (2003) Peptide mimics of peroxidase with anti-cataract activity. Dissertation, University of Jilin, pp 65–70
  3. Wang JY, Zhu SG, Xu CF (2002) Biochemistry, 3rd edn. Higher education press, Beijing, pp 174, 402–405

Cited by

See all 36

Metadata

Authors
Dong, Q.-G., Zhang, Y., Wang, M.-S., Feng, J., Zhang, H.-H., Wu, Y.-G., Gu, T.-J., Yu, X.-H., Jiang, C.-L., Chen, Y., Li, W., & Kong, W.
Affiliations
Jilin University (CN)
Corresponding author
  • Chen, Yan
  • Kong, Wei
ORCID
Venue
Amino Acids
Publisher
Springer Science and Business Media LLC
Published
2012-06-07
Volume
43
Issue
6
Pages
2431-2441
ISSN
  • 0939-4451 (ISSN-L)
  • 1438-2199
DOI
10.1007/s00726-012-1322-y
OpenAlex
W2076248750
Cited by
36
References
35
Citations by year
2026: 1 · 2025: 2 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 5 · 2014: 3
FWCI
0.96
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Amino Acids (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • China Postdoctoral Science Foundation
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
N-methylation, reactive oxygen species scavenging, hydrogen peroxide scavenging, intestinal permeability, oral drug delivery, enzymatic stability, proteolysis, Caco-2 cell monolayers, everted gut sac
MeSH terms
Animals, Enzyme Stability, Hemin, Humans, Intestinal Mucosa, Methylation, Peroxidase, Oligopeptides, Permeability, Substrate Specificity, Caco-2 Cells, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.