Poly(amidoamine)s with 2‐Dithiopyridine Side Substituents as Intermediates to Peptide–Polymer Conjugates

Abstract

Cystamine, when employed as a cross‐linking agent, leads to poly(amidoamine) networks, which on reaction with 2,2′‐dithiodipyridine turn into linear poly(amidoamine)s with side dithiopyridyl groups that easily undergo exchange reactions with reduced L‐glutathione, a model thiol‐containing biologically active peptide. The resultant products represent the first examples of soluble poly(amidoamine)–peptide conjugates in which the peptide moieties are linked to the polymer chain by SS bonds stable in blood, but cleavable inside cells.magnified image

Sterically stabilized self-assembling reversibly cross-linked polyelectrolyte complexes with nucleic acids for environmental and medical applications

“…Our twocomponent self-assembling system was an ideal starting point, as disulfide bonds can be formed readily by reacting a reduced thiol group with a thiol group activated by 2-thiopyridine. The introduction of thiol groups was readily accomplished by a new PAA polymer synthesis where some of the aminic component was replaced by a mono-Boc (tbutoxycarbonyl)-protected cystamine [15]. This disulfidecontaining polymer can then be readily converted into either the reduced thiol-or thiopyridyl-substituted polymer.…”

Polyamidoamines: Versatile Bioactive Polymers with Potential for Biotechnological Applications

“…These products were amenable to coupling reactions with thiolated peptides, such as for instance glutathione [39], and thiocholesterol [40]. In the latter instance, amphiphilic polymers were obtained giving spontaneously in aqueous media nano-aggregates that collapsed in the presence of reducing agents (Fig.…”

Poly(amidoamine)s: Past, present, and perspectives

“…Therefore, the aggregates are liable to collapse in reducing environments, as for instance after internalization in cells. PAA conjugates of SH‐bearing peptides, such as glutathione, were also prepared by the same technique [Scheme (d)] …”

“…The aggregation property is shared by other PAAs containing hydrophilic and hydrophobic moieties, 68 but in the above derivatives the hydrophobic moieties are linked to the PAA chain by SAS reductively cleavable bonds. Therefore, the aggregates are liable to collapse in reducing 102,103 Polymers bearing SAS bonds in the polymer chain are selectively degraded after cell internalization. When orally administered, the same polymers are stable in the first sections of the gastrointestinal tract, but degrade in the colon.…”