3 research outputs found
Orthogonal Cysteine–Penicillamine Disulfide Pairing for Directing the Oxidative Folding of Peptides
Precise
disulfide pairing in synthetic peptides usually is achieved
using orthogonal protecting group strategies or relies on primary
sequence manipulation. Orthogonal disulfide pairing technology should
be promising for directing the rational folding of multicyclic peptides
from the fully reduced peptides. Here, we report a discovery on the
orthogonality between heterodisulfide pairing of cysteine (Cys) and
penicillamine (Pen) and formation of Cys-Cys/Pen-Pen homodisulfides.
The orthogonal Cys-Pen disulfide pairing can be exploited for highly
selective production of certain (multi)Âcyclic structures (or even
a sole structure without isomers) through direct oxidation in air
or thiol–disulfide exchanges in redox media. This strategy
makes rational folding of multicyclic peptides without protecting
groups, sequence manipulation, and complex synthetic reactions a reality,
thus providing invaluable assets to peptide communities, and should
greatly benefit the development of multicyclic peptide therapeutics
and ligands
Proteolytic Unlocking of Ultrastable Twin-Acylhydrazone Linkers for Lysosomal Acid-Triggered Release of Anticancer Drugs
Targeted prodrugs
exploiting cleavable linkers capable of responding
to endogenous stimuli have increasingly been explored for cancer therapy.
Successful application of these prodrug designs relies on the manipulation
of both stability and responsiveness of the cleavable linkers, which,
however, are difficult to be finely regulated, particularly for acid-responsive
acylhydrazone bonds. Here we developed a new class of peptide-bridged
twin-acylhydrazone linkers (PTA linkers) displaying both an ultrahigh
stability and a rapid responsivenessî—¸highly stable in neutral
and acidic conditions due to the effect of cooperativity between the
two acylhydrazone bonds, easily cleavable in acidic conditions after
enzymatically triggered unlocking of the two bonds. Moreover, our
study shows the design of PTA-linked prodrugs and the proof-of-concept
application of the PTA linkers for site-specific release of anticancer
drugs into cancer cells
MOESM1 of Self-reported questionnaire survey on the prevalence and symptoms of adverse food reactions in patients with chronic inhalant diseases in Tangshan city, China
Additional file 1. Self-reported questionnaire survey on the prevalence and symptoms of food adverse reactions in patients with asthma, rhinitis and conjunctivitis. The questionnaire was developed referring to [1]