1. Separation of peptides by HPLC using a surface-confined ionic liquid stationary phase
K R Chitta, D S Van Meter, A M Stalcup Anal Bioanal Chem. 2010 Jan;396(2):775-81. doi: 10.1007/s00216-009-3228-4. Epub 2009 Oct 31.
A butylimidazolium bromide surface-confined ionic liquid stationary phase was synthesized in-house. The synthesized phase was investigated for the separation of five peptides (Gly-Tyr, Val-Tyr-Val, leucine enkephalin, methionine enkephalin, and angiotensin-II). The peptides were successfully separated in less than 5 min. The effect of trifluoroacetic acid (TFA) on the separation of peptides was evaluated with results confirming that TFA was not acting as ion-pairing agent in separation of peptides on this phase.
2. Effect of protease inhibitors on pulmonary bioavailability of therapeutic proteins and peptides in the rat
Kiran Prakash Amancha, Alamdar Hussain Eur J Pharm Sci. 2015 Feb 20;68:1-10. doi: 10.1016/j.ejps.2014.11.008. Epub 2014 Nov 21.
The objective of the present study was to evaluate the effect of protease inhibitors on the pulmonary absorption of therapeutic peptides and proteins with varying molecular weights. Dry powder formulations of leuprolide (1.2 kD), salmon calcitonin (3.4 kD), human insulin (5.8 kD), human leptin (16.0 kD), and human chorionic gonadotropin (HCG) (36.5 kD) were prepared with or without protease inhibitors; aprotinin and bestatin. The formulations were administered intrapulmonary to anesthetized rats. The pharmacokinetics of these proteins were assessed by measuring serum drug concentrations. In addition, in vitro stability of these proteins in rat lung homogenate was assessed using the trifluoroacetic acid method. Bioavailability of leuprolide following pulmonary administration was 75% higher compared to subcutaneously administered leuprolide. Protease inhibitors had little or no effect on the pulmonary bioavailability of leuprolide. However, protease inhibitors (1 mg/kg) increased the bioavailability of calcitonin by more than 50%. Similarly, the bioavailabilities of leptin and HCG in the presence of bestatin were increased by 1.9 and 2.1-fold, respectively. Leuprolide was stable both in the lung cytosol and subcellular pellets with about 10% degradation at the end of the study period (4h). In contrast, calcitonin, insulin, leptin and HCG were significantly degraded in the lung cytosol and subcellular pellets. Presence of protease inhibitors in formulation could improve the stability of protein drugs. The results of this study demonstrate that the pulmonary absorption of proteins may be enhanced by the selection of optimal concentration and type of protease inhibitor.
3. Ortho-Deuteration of Aromatic Aldehydes via a Transient Directing Group-Enabled Pd-Catalyzed Hydrogen Isotope Exchange
Junhua Kong, Zhi-Jiang Jiang, Jiayuan Xu, Yan Li, Hong Cao, Yanan Ding, Bencan Tang, Jia Chen, Zhanghua Gao J Org Chem. 2021 Oct 1;86(19):13350-13359. doi: 10.1021/acs.joc.1c01411. Epub 2021 Sep 13.
A practical and scalable ortho-selective deuteration of aromatic aldehydes was accomplished by Pd-catalyzed hydrogen isotope exchange with deuterium oxide as an inexpensive deuterium source. The use of tert-leucine as a transient directing group facilitates the exchange, affording a wide range of ortho-deuterated aromatic aldehydes with deuterium incorporation up to 97%. The control experiments suggest that the addition of silver trifluoroacetate resists the unexpected reduction of Pd(II), while the theoretical study indicates a rapid reversible concerted metalation-deprotonation process.
