PMID- 26456655
OWN - NLM
STAT- MEDLINE
DCOM- 20160218
LR  - 20151028
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 467
IP  - 3
DP  - 2015 Nov 20
TI  - New synthetic peptide with efficacy for heparin reversal and low toxicity and 
      immunogenicity in comparison to protamine sulfate.
PG  - 497-502
LID - S0006-291X(15)30724-5 [pii]
LID - 10.1016/j.bbrc.2015.10.020 [doi]
AB  - Protamine sulfate (PS), the only clinically approved antidote to unfractionated 
      heparin (UFH), is widely used for cardiopulmonary surgery or other extracorporeal 
      circulation situations. However, the applications of PS have accompanied various 
      severe side-effects. In this study, we presented a novel synthesized peptide 
      compound (RRRRR-RRRRR-RRRRR-sulfate, R15S) served as a safer UFH antidote. 
      Comparison studies were conducted between PS and R15S on efficacy and safety, 
      aided by heparin neutralization studies, drug toxicity studies and anaphylactic 
      analysis. Our research demonstrated that R15S contained comparable UFH 
      neutralization activity in vitro and in rats in vivo as to active partial 
      thromboplastin time (APTT) and anti-FXa assays. There was no cytotoxicity for 
      R15S at 60 mug mg(-1) or below and the median lethal dose (LD50) of R15S in mice 
      was 35.4 mg kg(-1), both of which were similar to that of PS. Furthermore, R15S 
      exhibited no immunogenicity while it was obvious in guinea pigs immunized with 
      PS. The level of cross-reactivity to anti-PS antibodies of R15S was about 30%. 
      Both of which indicated much safer properties of R15S than PS. In conclusion, we 
      presented a promising candidate R15S for UFH reversal, which is effective in 
      neutralizing UFH and potentially safer in use.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Li, Tong
AU  - Li T
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Meng, Zhiyun
AU  - Meng Z
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Zhu, Xiaoxia
AU  - Zhu X
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Gan, Hui
AU  - Gan H
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Gu, Ruolan
AU  - Gu R
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Wu, Zhuona
AU  - Wu Z
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Li, Jian
AU  - Li J
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Zheng, Ying
AU  - Zheng Y
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Liu, Taoyun
AU  - Liu T
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Han, Peng
AU  - Han P
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Han, Su
AU  - Han S
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China.
FAU - Dou, Guifang
AU  - Dou G
AD  - State Key Laboratory of Drug Metabolism, Laboratory of Hematological 
      Pharmacology, Beijing Institute of Transfusion Medicine, China. Electronic 
      address: douguifang@vip.sina.com.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151009
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Peptides)
RN  - 0 (Protamines)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Female
MH  - Heparin/*metabolism
MH  - Male
MH  - Peptides/*pharmacology/toxicity
MH  - Protamines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Cross-reactivity
OT  - Heparin neutralization
OT  - Immunogenicity
OT  - Protamine
OT  - Protamine toxicity
EDAT- 2015/10/13 06:00
MHDA- 2016/02/19 06:00
CRDT- 2015/10/13 06:00
PHST- 2015/09/03 00:00 [received]
PHST- 2015/10/04 00:00 [accepted]
PHST- 2015/10/13 06:00 [entrez]
PHST- 2015/10/13 06:00 [pubmed]
PHST- 2016/02/19 06:00 [medline]
AID - S0006-291X(15)30724-5 [pii]
AID - 10.1016/j.bbrc.2015.10.020 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2015 Nov 20;467(3):497-502. doi: 
      10.1016/j.bbrc.2015.10.020. Epub 2015 Oct 9.