RESUMEN
hPYY(3-36) injections have shown positive effects on appetite regulations, sparking increased interest in hPYY(3-36) research. Of great interest is oral delivery of hPYY(3-36) that can achieve clinically relevant weight-loss outcomes in what would be a highly patient compliant route. Successful oral delivery of other peptides utilizing the vitamin B12 pathway has been shown but below clinically relevant levels. Herein, we present clinically relevant in vivo oral delivery of B12-hPYY(3-36) conjugates.
Asunto(s)
Depresores del Apetito/administración & dosificación , Péptido YY/administración & dosificación , Vitamina B 12/administración & dosificación , Administración Oral , Animales , Depresores del Apetito/química , Depresores del Apetito/farmacocinética , Humanos , Fragmentos de Péptidos , Péptido YY/sangre , Péptido YY/química , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Vitamina B 12/sangre , Vitamina B 12/químicaRESUMEN
In the present paper, the authors focus on proton conduction pathways in a cubic perovskite KTaO(3) and an orthorhombic perovskite SrZrO(3). Density functional theory with a generalized gradient approximation is used to find proton binding sites. The nudged elastic band method is used to find transition states between minima. With this potential energy map of binding and transition states, adjacency matrices and their analogs identify four types of conduction paths in KTaO(3). Distortions from these paths are seen in SrZrO(3). In both cases, the lowest energy path has an intraoctahedral transfer rate-limiting barrier. A Fourier analysis of the OH stretch in ab initio molecular dynamics simulations revealed a strongly redshifted OH stretch in SrZrO(3) relative to KTaO(3). Hence, an orthorhombic system with a lowest energy conduction path limited by an intraoctahedral barrier can exhibit a redshifted OH stretch.
