Spectroscopic methods (IR, NMR AND CD) in conformational analysis of ferrocene peptides

Najveća zapreka za korištenje biološki aktivnih peptida u terapeutske svrhe je njihova konformacijska fleksibilnost koja može izazvati nuspojave uslijed vezanja na neželjene receptore. Kako bi se uz spomenuto prevladala i ostala ograničenja za terapeutsku primjenu peptida, dizajnirani su peptidomimetici. Ferocenski peptidomimetici građeni su iz ferocenskog kalupa na koji su vezane aminokiselinske sekvence, a svrha kalupa je indukcija elemenata sekundarne strukture i ''zaključavanje'' peptida u biološki aktivnoj konformaciji. U ovom radu opisana je konformacijska analiza homokiralnog tetrapeptida Ac-L-Ala-L-Pro-NH-Fn-NH-L-Pro-L-Ala-Boc (1) i njegovog dijastereomera, heterokiralnog peptida Ac-D-Ala-L-Pro-NH-Fn-NH-L-Pro-D-Ala-Boc (2). Kao kalup, na kojeg su vezani Pro-Ala peptidi koji se međusobno razlikuju u kiralnosti alaninskog ostatka, upotrijebljen je ferocen-1,1'-diamin (Fcda). Strukturna analiza tih peptidomimetika provedena je mjerenjem IR-spektara (ovisno o koncentraciji), te NMR-spektara (ovisno o koncentraciji, temperaturi i otapalu) i CD-spektara. Cilj ovog rada jest prikazati upotrebu spektroskopskih metoda u konformacijskoj analizi ferocenskih peptida te ukazati na utjecaj kiralnosti peptidne okosnice na njihova konformacijska svojstva.The greatest obstacle for clinical usage of peptides is their conformational flexibility capable to cause side effects due to the binding to undesired receptors. To overcome all the limitations for the therapeutic application of peptides, peptidomimetics have been designed. Ferrocene peptidomimetic is composed of a ferrocene scaffold equipped with peptide strands, aimed to induce secondary structure elements and to lock peptide in a biologically active conformation. Herein, a conformational analysis of the homochiral tetrapeptide Ac-L-Ala-L-Pro-NH-Fn-NH-L-Pro-L-Ala-Boc (1) and its diastereomeric heterochiral peptide Ac-D-Ala-L-Pro-NH-Fn-NH-L-Pro-D-Ala-Boc (2) is described. Ferrocene-1,1'-diamine (Fcda) was used as the scaffold for attachment of Pro-Ala sequences which differ in the chirality of alanine unit Structural analysis of these peptidomimetics was performed by measuring of IR (concentration-dependent), NMR (concentration-, temperature- and solvent-dependent) and CD spectra. The goal of this work is to present the application of the spectroscopic methods in the conformational analysis of ferrocene peptides and to point out the impact of the peptide backbone chirality on its conformational properties