In This Issue, Volume 9, Issue 5

EFFICIENT SYNTHESES OF COCAINE VACCINES 3 AND THEIR IN VIVO EVALUATION 4 Cocaine addiction and abuse remain major health and societal 5 issues in the United States. Despite this, no therapeutic treat- 6 ment for cocaine addiction is available and current interventions 7 only address withdrawal symptoms interventions. 8 In this issue, Janda and colleagues (DOI: 10.1021/acsmedchem- 9 lett.8b00051) present the development and in vivo evaluation of 10 two cocaine vaccines. Each vaccine consists of one of two hydro- 11 lytically stable haptens developed previously by the researchers, 12 GND or GNE, conjugated to tetanus toxoid (TT) and formulated 13 with alum and cytosine-guanine oligonucleotide (CpG ODN 14 1826) adjuvants. Both vaccines, termed GND-TT and GNE-TT, 15 triggered the production of antibodies with high affinity for 16 cocaine in mice, and these newly generated antibodies success- 17 fully blocked the stimulatory activity of cocaine. Biodistribution 18 studies revealed the ability of GND-TT and GNE-TT to seques- 19 ter free cocaine in the blood and to reduce the drug’s concen- 20 tration in the brain. These results suggest that GND- and GNE-TT g 21 conjugates are suitable for further preclinical development. SYNTHESIS OF PHOSPHATIDYLSERINE AND ITS 23 STEREOISOMERS: THEIR ROLE IN ACTIVATION OF 24 BLOOD COAGULATION 25 Blood coagulation is initiated by the formation of a complex 26 between a transmembrane protein called tissue factor (TF) and 27 circulatory factor VIIa (FVIIa). Phosphatidylserine facilitates this 28 process; however, the mechanism by which this occurs remains 29 enigmatic. Herein, Mallik et al. (DOI: 10.1021/acsmedchem- 30 lett.8b00008) report the synthesis of all stereoisomers of 31 phosphatidylserine (PS) using a novel synthetic method and 32 subsequent studies of each phosphatidylserine isomer with 33 circulatory factor VIIa and tissue factor TF. An assay involving 34 recombinant FVIIa and full length TF present in a reconstituted 35 membrane model revealed that the configuration of both the 36 headgroup and the glycerol backbone of PS play a role in enhanced 37 TF-FVIIa complex activity. The authors also performed molecular 38 dynamics simulations and suggest that changes in chiral centers 39 affect the interactions between the PS head groups and glycerol 40 backbone with TF and FVIIa. 41 This study thus provides new insights into structure−activity 42 relationship and protein−lipid interactions in the blood g 43 coagulation. In This Issue