Cathepsin B & Synthetic Substrates

T. Chyau Liang tliang at
Wed May 29 04:05:01 EST 1996

>   It is much easier to synthesise alpha-N-acyl-Arg derivatives than the
> corresponding Lys ones-because of acylation of epsilon NH2 as well as alpha
> NH2.

True and this may be the historical reason (I guess??) why Acy-Arg
derivatives are often used.  Fortunately, nowadys you can buy either alpha
or epsilon protected Lys and let other people worry about the synthtic

I think the following point is probably more important. One example is
thrombin, which prefers Arg to Lys at P1 by a factor of 100 or larger. On
the other hand, plasmin prefers Lys to Arg at P1.

>   And of course, some enzymes, eg trypsin, do not discriminate between R and 
> K (at P1). Others however _DO_ discriminate.  I don't at what level you've 
> looked at the crystal structure - but discrimination can depend on subtle 
> features of the geometry of the enzyme subsite and the position of the D/E 
> within in it.
>   In other words, if you're looking at the structure and saying, "well
> the subsite, and there's a negative charge at the bottom," then that's
not close
> to being enough information to form an opinion as to whether K or R or either
> derivatives should be recognised.

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