 |
PDBsum entry 6twc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Blood clotting
|
PDB id
|
|
|
|
6twc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
De novo development of proteolytically resistant therapeutic peptides for oral administration.
|
|
|
Authors
|
|
X.D.Kong,
J.Moriya,
V.Carle,
F.Pojer,
L.A.Abriata,
K.Deyle,
C.Heinis.
|
|
|
Ref.
|
|
Nat Biomed Eng, 2020,
4,
560-571.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The oral administration of peptide drugs is hampered by their metabolic
instability and limited intestinal uptake. Here, we describe a method for the
generation of small target-specific peptides (less than 1,600 Da in size) that
resist gastrointestinal proteases. By using phage display to screen large
libraries of genetically encoded double-bridged peptides on protease-resistant
fd bacteriophages, we generated a peptide inhibitor of the coagulation Factor
XIa with nanomolar affinity that resisted gastrointestinal proteases in all
regions of the gastrointestinal tract of mice after oral administration,
enabling more than 30% of the peptide to remain intact, and small quantities of
it to reach the blood circulation. We also developed a
gastrointestinal-protease-resistant peptide antagonist for the interleukin-23
receptor, which has a role in the pathogenesis of Crohn's disease and ulcerative
colitis. The de novo generation of targeted peptides that resist proteolytic
degradation in the gastrointestinal tract should help the development of
effective peptides for oral delivery.
|
|
|
|
|
|
|
