2 research outputs found
Local Control of the <i>Cis</i>–<i>Trans</i> Isomerization and Backbone Dihedral Angles in Peptides Using Trifluoromethylated Pseudoprolines
NMR studies and theoretical calculations have been performed on model peptides Ac-Ser(ΨPro)-NHMe, (<i>S</i>,<i>S</i>)Ac-Ser(Ψ<sup>H,CF3</sup>Pro)-NHMe, and (<i>R,S</i>)Ac-Ser(Ψ<sup>CF3,H</sup>Pro)-NHMe. Their thermodynamic and kinetic features have been analyzed in chloroform, DMSO, and water, allowing a precise description of their conformational properties. We found that trifluoromethyl C<sup>δ</sup>-substitutions of oxazolidine-based pseudoprolines can strongly influence the <i>cis</i>–<i>trans</i> rotational barriers with only moderate effects on the <i>cis</i>/<i>trans</i> population ratio. In CHCl<sub>3</sub>, the configuration of the CF<sub>3</sub>–C<sup>δ</sup> entirely controls the ψ-dihedral angle, allowing the stabilization of γ-turn-like or PPI/PPII-like backbone conformations. Moreover, in water and DMSO, this C<sup>δ</sup>-configuration can be used to efficiently constrain the ring puckering without affecting the <i>cis</i>/<i>trans</i> population ratio. Theoretical calculations have ascertained the electronic and geometric properties induced by the trifluoromethyl substituent and provided a rational understanding of the NMR observations
Multivalent Interactions: Synthesis and Evaluation of Melanotropin MultimersTools for Melanoma Targeting
To develop agents for early detection and selective treatment
of melanomas, high affinity and high specificity molecular tools are
required. Enhanced specificity may be obtained by simultaneously binding
to multiple cell surface targets via the use of multimeric analogues
of naturally occurring ligands. Trimers targeting overexpressed melanocortin
receptors have been found to be potential candidates for this purpose.
In the present letter, we describe the synthesis and study of multimers
based on a dendrimer-like scaffold. The binding affinity and activity
results revealed that dendrimers promote multivalent interactions
via statistical and/or cooperative effects on binding. Moreover, viability
studies showed no significant toxicity at micromolar concentrations,
which will allow these molecular complexes to be used in vivo. Finally,
imaging studies showed effective internalization for all of the molecules,
confirming their potential as delivery agents