scholarly journals Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes

2021 ◽  
Vol 7 (45) ◽  
Author(s):  
Maxime Killer ◽  
Jiri Wald ◽  
Joanna Pieprzyk ◽  
Thomas C. Marlovits ◽  
Christian Löw
2021 ◽  
Author(s):  
Maxime Killer ◽  
Jiri Wald ◽  
Joana Pieprzyk ◽  
Thomas C Marlovits ◽  
Christian Loew

The uptake of peptides in mammals plays a crucial role in nutrition and inflammatory diseases. This process is mediated by promiscuous transporters of the Solute Carrier Family 15, which form part of the Major Facilitator superfamily. Besides the uptake of short peptides, Peptide transporter 1 (PepT1) is a highly abundant drug transporter in the intestine and represents a major route for oral drug delivery. Peptide transporter 2 (PepT2) allows in addition renal drug reabsorption from ultrafiltration and brain-to-blood efflux of neurotoxic compounds. Here we present cryo-EM structures of human PepT1 in an outward open state and of human PepT2 in an inward facing partially occluded state with a bound substrate. The structures reveal the architecture of human peptide transporters and provide mechanistic insights into substrate recognition and conformational transitions during transport. Importantly, this may support future drug design efforts to increase the bioavailability of different drugs in the human body.


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
C Tarirai ◽  
A Viljoen ◽  
P Chinyemba ◽  
A Khatib ◽  
P Jiyane ◽  
...  

2020 ◽  
Vol 25 (42) ◽  
pp. 4464-4485 ◽  
Author(s):  
Katarzyna Kluszczyńska ◽  
Liliana Czernek ◽  
Wojciech Cypryk ◽  
Łukasz Pęczek ◽  
Markus Düchler

Background: Exosomes open exciting new opportunities for advanced drug transport and targeted release. Furthermore, exosomes may be used for vaccination, immunosuppression or wound healing. To fully utilize their potential as drug carriers or immune-modulatory agents, the optimal purity of exosome preparations is of crucial importance. Methods: Articles describing the isolation and purification of exosomes were retrieved from the PubMed database. Results: Exosomes are often separated from biological fluids containing high concentrations of proteins, lipids and other molecules that keep vesicle purification challenging. A great number of purification protocols have been published, however, their outcome is difficult to compare because the assessment of purity has not been standardized. In this review, we first give an overview of the generation and composition of exosomes, as well as their multifaceted biological functions that stimulated various medical applications. Finally, we describe various methods that have been used to purify small vesicles and to assess the purity of exosome preparations and critically compare the quality of these evaluation protocols. Conclusion: Combinations of various techniques have to be applied to reach the required purity and quality control of exosome preparations.


Author(s):  
Marieta Constantin ◽  
Sanda Bucatariu ◽  
Irina Popescu ◽  
Bogdan Cosman ◽  
Paolo Ascenzi ◽  
...  

Author(s):  
Stefanie Kennon‐McGill ◽  
Mitchell R. McGill
Keyword(s):  

2018 ◽  
Vol 6 (39) ◽  
pp. 6269-6277 ◽  
Author(s):  
Yaya Cheng ◽  
Xiangyu Jiao ◽  
Liang Zhao ◽  
Yang Liu ◽  
Fang Wang ◽  
...  

Inspired by aquaporins in nature, herein, a biomimetic free-blocking on-demand drug delivery system is proposed, which is constructed by controlling the wettability of the inner surface of nanochannels on mesoporous silica nanoparticles (MSNs).


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