Papain Inhibitors

It will be interesting to follow the development of surface-bound electrochemical protein sensors based on metallocene-peptide conjugates. 

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LaLonde JM, Zhao B, Smith WW, Janson CA, DesJarlais RL, Tomaszek TA, Carr TJ, Thompson SK, Oh HJ, Yamashita DS, Veber DF, Abdel-Meguid SS. Use of papain as a model for the structure-based design of cathepsin K inhibitors crystal structures of two papain-inhibitor complexes demonstrate binding to S -subsites. J Med Chem 1998 41 4567-4576. 

Gottschlich et al. [26] described the separation of tetramethyl rhodamine isothiocyanate (TRITC)-labeled tryptic peptides of (3-casein. The field strength was 220 V/cm in the NCEC channel with lOmM sodium borate with 30% (v/v) acetonitrile as mobile phase. Throckmorton et al. [27] described the separation of papain inhibitor, proctolin, opioid peptide (a-casein fragment 90-95), Ile-angiotensin III and angiotensin III on a porous polymer monolith... 

Figure 7.9 Chromatogram of (1) papain inhibitor, (2) proctolin, (3) opioid peptide (a-casein fragment 90-95), (4) Ile-angiotensin HI, (5) angiotensin HI, and (6) GGG [27],...

Chapter 5). Separation of a mixture of BODIPY and fluorescein was achieved in less than 20 s (see Figure 6.23). Five bioactive peptides (papain inhibitors, proctobin, opioid fragment 90-95, ileangiotensin HI, and angiotensin III) were also separated in this manner [639]. A similar method has been used to separate two coumarin dyes or to separate Alexafluor-labeled angiotensin from the excess dye [587,640]. CEC separation of four FITC-labeled synthetic peptides was... 

Thiol proteinase (papain) inhibitor 12,700 Papain, ficin, cathepsin B 22, 21... 

Guo, W. and Ruckenstein, E., Crosslinked mercerized cellulose membranes for the affinity chromatography of papain inhibitors, J. Membr. ScL, 197, 53, 2002. 

The ferrocene 44 bearing only one tetrapeptide chain (-Gly-Gly-L-Tyr-L-Arg-OH) is designed to bind to papain [147]. The ferrocene 44 acts as an efficient competitive papain inhibitor for AT-benzoylarginine ethyl ester hydrolysis, with an inhibition constant Ki of 9 xM at pH 6.2. Binding of papain to the ferrocene receptor 44 causes an electrochemical response, resulting in a small cathodic shift of the redox potential of the ferrocene moiety of 44. 

The U-4CR of lOw, 6zb, 9d, and Ize provided the Ugi product 278, which under acidic conditions afforded the key intermediate A(-acylpyrrole 279 (Scheme 7.88). In the presence of various nucleophiles, 279 afforded amides (280 and 281) and methyl ester 282 under refluxing conditions in good yields. In the presence of LiOH, 279 afforded the acid 283 at room temperature in an excellent yield. Employment of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), NaBH4, and Homer-Wadsworth-Emmons conditions provided the aldehyde 284, alcohol 285, and the a,p-unsaturated ester 286, respectively. These synthetic transformations can be very useful in particular, compound 286 is a valuable intermediate for the synthesis of 3-aza-bicyclo[3.1,0]hexane ring system, constrained amino acids, papain inhibitors, ( )-isocynodine, and ( )-isocynometrine [102],... 

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