精氨酸取代的新型合成肽及其应用

摘要

本发明涉及根据人体乳铁蛋白序列设计的精氨酸取代的新肽及其应用，尤其是用于治疗和/或预防感染、炎症、肿瘤、疼痛、创伤和/或伤痕的肽。

主权项

一种如式(1)所示的肽：R1-Phe-X1-X2-X3-X4-X5-X6-X7-Lys-Val-Arg-X8-R2                                        |α                                        R3    式(1)其中，氨基酸X1是Gln或Ala，氨基酸X2是Trp或Leu，氨基酸X3是Gln、Ala、Orn、Nle或Lys，氨基酸X4是Arg、Ala或Lys，氨基酸X5是Asn、Ala、Orn或Nle，氨基酸X6是Met、Ala或Leu，氨基酸X7是Arg、Ala或Lys，氨基酸X8是Gly、Lys、Glu或Asp；当X8是Gly时，则R3是Ser-(Arg)n-X9且键α是Gly的羧基与Ser的氨基之间的肽键；当X8是Lys时，则R3是X9-(Arg)n-Ser且键α是Lys的ε-氨基与Ser的羧基之间的酰胺键；和当X8是Glu或Asp时，则R3是Ser-(Arg)n-X9且键α是Glu的γ-羧基或Asp的β-羧基与Ser的氨基之间的酰胺键；氨基酸X9位无氨基酸或者是Gly；且n是1-10的整数，优选2-6的整数，优选4-6的整数，或更优选3-4的整数；R1位无氨基酸、或者是Cys、或者是选自SEQ ID NO：3所示的肽及其切除了N末端的片段的肽中的肽序列，所述肽序列包括：Gly-Arg-Arg-Arg-Arg-Ser-Val-Gln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，    Arg-Arg-Arg-Arg-Ser-Val-Gln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，        Arg-Arg-Arg-Ser-Val-Gln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，            Arg-Arg-Ser-Val-G ln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，                Arg-Ser-Val-Gln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，                    Ser-Val-Gln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，                        Val-Gln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，                            Gln-Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，Trp-Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，    Cys-Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，        Ala-Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，            Val-Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，                Ser-Gln-Pro-Glu-Ala-Thr-Lys-Cys，                    Gln-Pro-Glu-Ala-Thr-Lys-Cys，                        Pro-Glu-Ala-Thr-Lys-Cys，                            Glu-Ala-Thr-Lys-Cys，                                Ala-Thr-Lys-Cys，                                    Thr-Lys-Cys，                                            和                                        Lys-Cys，R2位无氨基酸，或者是Pro，或者是选自SEQ ID NO：4所示的肽及其切除了C末端的片段的肽中的肽序列，所述肽序列包括：Pro-Pro-Val-Ser-Cys-Ile-Lys-Arg，Pro-Pro-Val-Ser-Cys-Ile-Lys，Pro-Pro-Val-Ser-Cys-Ile，Pro-Pro-Val-Ser-Cys，Pro-Pro-Val-Ser，Pro-Pro-Val，andPro-Pro，。