中国抗生素杂志
中國抗生素雜誌
중국항생소잡지
CHINESE JOURNAL OF ANTIBIOTICS
2010年
4期
300-304
,共5页
李勇湧%黄文祥%朱卫民%李崇智%张德梅
李勇湧%黃文祥%硃衛民%李崇智%張德梅
리용용%황문상%주위민%리숭지%장덕매
β-内酰胺酶%酶动力学%β-内酰胺酶抑制肽
β-內酰胺酶%酶動力學%β-內酰胺酶抑製肽
β-내선알매%매동역학%β-내선알매억제태
β-lactamase%Enzyme kinetic%β-lactamase inhibitory peptide
目的 通过合成和筛选具有一定抑酶作用的β-内酰胺酶抑制肽,考察其抑制活性及抑制动力学生化特征,以用于产β-内酰胺酶耐药菌所致感染的临床治疗.方法 固相合成法在计算机上三维模拟设计合成β-内酰胺酶抑制肽.选取我院08年临床分离鉴定的产酶菌8株,测定临床常用抗生素对8株细菌的MIC值,采用试管稀释法进行β-内酰胺酶抑制肽活性初步筛选.分光光度法研究抑制肽对8株产酶菌所产β-内酰胺酶的抑酶效力,Dixon作图法求取抑制常数K_i,计算相关抑制动力学参数.结果 合成了6段系列短肽分子,筛选得到3段具有抑制活性的抑制肽,抑制底物动力学研究验证3段β-内酰胺酶抑制肽具有一定抑制活性,但抑制常数均较大,其抑制方式均为竞争性抑制.结论 3段具有抑制活性的β-内酰胺酶抑制肽的抑制活性均较弱.
目的 通過閤成和篩選具有一定抑酶作用的β-內酰胺酶抑製肽,攷察其抑製活性及抑製動力學生化特徵,以用于產β-內酰胺酶耐藥菌所緻感染的臨床治療.方法 固相閤成法在計算機上三維模擬設計閤成β-內酰胺酶抑製肽.選取我院08年臨床分離鑒定的產酶菌8株,測定臨床常用抗生素對8株細菌的MIC值,採用試管稀釋法進行β-內酰胺酶抑製肽活性初步篩選.分光光度法研究抑製肽對8株產酶菌所產β-內酰胺酶的抑酶效力,Dixon作圖法求取抑製常數K_i,計算相關抑製動力學參數.結果 閤成瞭6段繫列短肽分子,篩選得到3段具有抑製活性的抑製肽,抑製底物動力學研究驗證3段β-內酰胺酶抑製肽具有一定抑製活性,但抑製常數均較大,其抑製方式均為競爭性抑製.結論 3段具有抑製活性的β-內酰胺酶抑製肽的抑製活性均較弱.
목적 통과합성화사선구유일정억매작용적β-내선알매억제태,고찰기억제활성급억제동역학생화특정,이용우산β-내선알매내약균소치감염적림상치료.방법 고상합성법재계산궤상삼유모의설계합성β-내선알매억제태.선취아원08년림상분리감정적산매균8주,측정림상상용항생소대8주세균적MIC치,채용시관희석법진행β-내선알매억제태활성초보사선.분광광도법연구억제태대8주산매균소산β-내선알매적억매효력,Dixon작도법구취억제상수K_i,계산상관억제동역학삼수.결과 합성료6단계렬단태분자,사선득도3단구유억제활성적억제태,억제저물동역학연구험증3단β-내선알매억제태구유일정억제활성,단억제상수균교대,기억제방식균위경쟁성억제.결론 3단구유억제활성적β-내선알매억제태적억제활성균교약.
Objective To synthesize and screen β-lactamase inhibitory peptides which have certain inhibitory effect to β-lactamase.To detect the kinetics of biochemical characteristics and its inhibitory activity for the treatment of clinical infection caused by bacterium which producing β-lactamase.Methods β-lactamase inhibitory peptide were three-dimensional designed and synthesized by solid phase synthesis method with computer.Eight clinical β-lactamase-producing isolates were selected in 2008 from our hospital.Their MIC to clinical commonly used antibiotics were tested.Tube-dilution-test was used for screening the activity of β-lactamase inhibitory peptide.The inhibitory activity of 3 β-lactamase inhibitory peptide to β-lactamase produced by the 8 bacteriums was studied with spectrophotometer.Inhibition constant(K_i)were obtained from dixon plot.And the relevance kinetic parameters of inhibition were calculated.Results A series of 6 short peptides were synthesized,3 inhibitory peptide with the inhibitory activity were selected.We found that 3 β-lactamase inhibitory peptides have a certain enzyme inhibitory activity through the calculation of substrate inhibition kinetics.But inhibition constant were all great.And all inhibition modes are competitive inhibition.Conclusion The inhibitory activities of 3 β-lactamase inhibitory peptides are weak.
