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p-id="1043"></path></svg> </a> </div> </div></div> </div><hr class="e_line-11 s_line" /><div class="e_container-12 s_layout"> <div class="cbox-12-0 p_item"><div class="e_richText-15 s_title clearfix myart"> <p>銆€銆€PROTAC(Proteolysis Targeting Chimera锛岃泲鐧介澏鍚戦檷瑙ｅ祵鍚堜綋)鏄€氳繃娉涚礌-铔嬬櫧閰朵綋绯荤粺璇卞闈跺悜铔嬬櫧闄嶈В鐨勪竴绉嶅叏鏂版妧鏈€侾ROTAC鍒嗗瓙鐢变笁閮ㄥ垎缁勬垚锛氶澏鍚戠粨鍚堢洰鏍囪泲鐧界殑閰嶄綋銆佹嫑鍕烢3娉涚礌杩炴帴閰剁殑閰嶄綋浠ュ強涓よ€呬箣闂寸殑杩炴帴閾?linker)銆侾ROTAC鍒嗗瓙涓庨澏铔嬬櫧鍜孍3娉涚礌杩炴帴閰跺舰鎴愮ǔ瀹氱殑涓夊厓澶嶅悎鐗╋紝E3娉涚礌杩炴帴閰朵负闈惰泲鐧借创涓婃硾绱犳爣绛撅紝娉涚礌鍖栫殑闈惰泲鐧借铔嬬櫧閰朵綋璇嗗埆骞堕檷瑙ｃ€傝€岄潪鍏变环PROTAC鍒嗗瓙鍙笌涓夊厓澶嶅悎鐗╄В绂伙紝浠庤€屽惊鐜娇鐢ㄣ€侟/p> <p>銆€銆€</p> <center><img src="https://omo-oss-image.thefastimg.com/portal-saas/new2023042821215034000/cms/image/57b1c2a6-823a-4bdf-9891-4de554af972c.png" style="width: 300px; height: 130px;" /></center> <center> </center> <p style="text-align: center;">Fig 1 PROTAC鍒嗗瓙缁勬垚鍙婁綔鐢ㄦ満鍒禰1]</p> <p style="text-align: center;"> </p> <p>銆€銆€PROTAC linker灏咵3娉涚礌杩炴帴閰堕厤浣撲笌闈惰泲鐧介厤浣撹繛鎺ヨ捣鏉ワ紝鍏朵腑linker鐨勮璁′笌閫夋嫨瀵逛簬PROTAC鍒嗗瓙鐨勬垚鑽€ч潪甯搁噸瑕併€侺inker鐨勭被鍨嬨€侀暱搴﹀拰杩炴帴浣嶇偣浼氬奖鍝峆ROTAC鐨勭粨鏋勫垰鎬с€佺枏姘存€у拰婧惰В鎬х瓑锛屼粠鑰屽奖鍝嶄笁鍏冨鍚堢墿鐨勫舰鎴愬強鏈€缁堢殑闄嶈В娲绘€с€侟/p> <p>銆€銆€PEG鏄疨ROTAC寮€鍙戜腑鏈€甯哥敤鐨刲inker锛屾嵁缁熻锛屽湪宸叉姤閬撶殑PROTAC鍒嗗瓙涓湁54%浣跨敤浜哖EG浣滀负linker[2]銆侟/p> <p>銆€銆€PEG linker鍦≒ROTAC涓殑浣滅敤锛欬/p> <p>銆€銆€1. PEG鐨勫紩鍏ュ彲浠ュ鍔燩ROTAC鍒嗗瓙鐨勬按婧舵€э紝褰卞搷缁嗚優娓楅€忔€э紝浠庤€屽奖鍝嶅彛鏈嶅惛鏀躲€侟/p> <p>銆€銆€2. 閫氳繃浣跨敤涓嶅悓閾鹃暱鐨凱EG鍙交鏉惧疄鐜板 linker闀垮害绯荤粺鎬х殑鏀瑰彉锛屽奖鍝峆ROTAC鍒嗗瓙鐨勯檷瑙ｆ晥鐜囥€侟/p> <p>銆€銆€3. 浣跨敤鍚勭鍙屽畼鑳藉寲鐨凱EG linker锛岃兘澶熺畝鍗曘€佸揩閫熷湴缁勮鍏锋湁涓嶅悓杩炴帴鍩哄洟鐨勫垎瀛愶紝鍔犻€熺瓫閫夊緱鍒版湁鏁堢殑闄嶈В缁撴瀯銆侟/p> <p>銆€銆€鐩歌緝浜庝紶缁熺殑灏忓垎瀛愭姂鍒跺墏锛孭ROTAC鎶€鏈湪娲绘€с€侀€夋嫨鎬с€侀澏鍚?ldquo;涓嶅彲鎴愯嵂”铔嬬櫧銆佸厠鏈嶈€愯嵂鎬у強鐢ㄨ嵂閫斿緞绛夋柟闈㈡洿鏈変紭鍔匡紝杩戝勾鏉ュ彂灞曡繀閫燂紝宸叉垚涓烘柊鑽爺鍙戜腑鐨勪竴澶у埄鍣ㄣ€傞敭鍑鎶€涓撴敞浜嶱ROTAC Linker鐨勭爺鍙戯紝鎻愪緵鍏锋湁鍚勭娲绘€у熀鍥㈢殑楂樼函搴EG linker锛屾寔缁姪鍔涙偍鐨勭爺鍙戦」鐩紑鍙戙€傞敭鍑鎶€鏈熷緟涓庢偍鍚堜綔!</p> <p> </p> <p>References:</p> <p>[1] Sun X, Gao H, Yang Y, et al. PROTACs: great opportunities for academia and industry. Signal Transduct Target Ther. 2019;4:64.</p> <p>[2] Troup RI, Fallan C, Baud MGJ. Current strategies for the design of PROTAC linkers: a critical review. 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