Schnur Einat, Rudd Timothy R
National Institute of Biological Standards and Control Blanche Lane, South Mimms Potters Bar Hertfordshire EN6 3QG UK
RSC Adv. 2020 Jul 29;10(47):28300-28313. doi: 10.1039/d0ra04204h. eCollection 2020 Jul 27.
Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that patients taking a low molecular weight heparin, dalteparin (DAL), and then prescribed, OXT experienced a swifter labour compared to women given OXT alone. Herein are described the interactions between OXT and a number of heparin-based oligosaccharides; DAL; fondaparinux (FP), which is a synthetic heparin oligosaccharide that represents the predominant antithrombin binding-site, and a family of chemically-derived heparin hexasaccharides. The latter oligosaccharides were chosen as they represent sequences found within the polysaccharide dalteparin. Furthermore, the carbohydrate chemical space was investigated by comparing the interaction between OXT and four chemically derivatived heparin hexasaccharides; I-A (DP6), I-A (DP6-2OH, de-2--sulfated hexasaccharide), I-A (DP6-6OH, de-6--sulfated hexasaccharide) and I-A (DP6-NAc, de--sulfated hexasaccharide). The interactions between the peptide and oligosaccharides were studied using a series of C-H and N-H HSQC NMR experiments, at a range of temperatures. This approach allowed the binding epitopes of the peptide and oligosaccharides to be identified, highlighting that 6-- and -sulfation substituent groups of heparin are important for the interaction between the peptide and carbohydrate. This is an important observation as de--sulfation is a traditional method for decreasing the anticoagulation properties of heparin. Furthermore, low temperature experiments of the OXT : FP complex indicate that hydrogen-bonding is very important for the interaction between the peptide and oligosaccharide.
催产素（OXT）是一种小的环状肽，在分娩延长的情况下用于给孕妇引产。此前观察到，服用低分子量肝素达肝素（DAL）后再使用催产素的患者，与仅使用催产素的女性相比，分娩过程更快。本文描述了催产素与多种基于肝素的寡糖之间的相互作用；达肝素；磺达肝癸钠（FP），它是一种合成肝素寡糖，代表主要的抗凝血酶结合位点，以及一族化学衍生的肝素六糖。选择后者寡糖是因为它们代表了在多糖达肝素中发现的序列。此外，通过比较催产素与四种化学衍生的肝素六糖之间的相互作用，研究了碳水化合物化学空间；I-A （DP6）、I-A （DP6-2OH，去-2-O-硫酸化六糖）、I-A （DP6-6OH，去-6-O-硫酸化六糖）和I-A （DP6-NAc，去-N-硫酸化六糖）。在一系列温度下，使用一系列C-H和N-H HSQC NMR实验研究了肽与寡糖之间的相互作用。这种方法能够鉴定肽和寡糖的结合表位，突出表明肝素的6-O-和N-硫酸化取代基对于肽与碳水化合物之间的相互作用很重要。这是一个重要的观察结果，因为去-N-硫酸化是降低肝素抗凝特性的传统方法。此外，催产素：磺达肝癸钠复合物的低温实验表明，氢键对于肽与寡糖之间的相互作用非常重要。
