New, potent, small molecule agonists of tyrosine kinase receptors attenuate dry eye disease.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this.

Small molecule peptidomimetic trypsin inhibitors: validation of an EKO binding mode, but with a twist.

Examination of a series of naturally-occurring trypsin inhibitor proteins, led to identification of a set of three residues (which we call the "interface triplet") to be determinant of trypsin binding affinity, hence excellent templates for small molecule mimicry. Consequently, we attempted to use the Exploring Key Orientation (EKO) strategy developed in our lab to evaluate small molecules that mimic the interface triplet regions of natural trypsin inhibitors, and hence potentially might bind and inhibit the catalytic activity of trypsin. A bis-triazole scaffold ("TT-mer") was the most promising of the molecules evaluated .

Prion inhibition with multivalent PrPSc binding compounds.

Quinacrine and related heterocyclic compounds have antiprion activity. Since the infectious pathogen of prion diseases is composed of multimeric PrP(Sc) assemblies, we hypothesized that this antiprion property could be enhanced by attaching multiple quinacrine-derived chloroquinoline or acridine moieties to a scaffold. In addition to exploring Congo red dye and tetraphenylporphyrin tetracarboxylic acid scaffolds, which already possess intrinsic prion-binding ability; trimesic acid was used in this role.