New challenge - Hinge-Linker

[AndrewCRMartin]

INN12138 is a mini-antibody using CH3 instead of a leucine zipper. The AbML is

VL(1:3)-L(2)-VH(3:1)-H*(4:10){2}[MOD:REMCYS][NOTE: Nter 5aa extension]-L(5:11){1}-CH3(6:12)|VL(7:9)-L(8)-VH(9:7)-H(10:4){2}[MOD:REMCYS][NOTE: Nter 5aa extension]-L(11:5){1}-CH3(12:6)

The hinge includes the last 5 residues of the CH1 and is modified to remove the cys that would normally disulphide with the Cter of the CL is mutated to Cys.

The linker that follows the hinger contains a cysteine to form an extra disulphide with the other chain.

Even if it can't be drawn on the app, it would be good to render it - I guess you could add a H-L (hinge-linker) join type (and a linker-hinge - L-H - at the same time). The H-L would appear as two separate things in the AbML, but a single button on the interface.

Good luck!

[AndrewCRMartin]

Actually I think this is a better description:

VL(1:3)-L(2)-VH(3:1)-H*(4:10){3}[MOD:REMCYS][NOTE: Nter 5aa extension Cter 2aa extension]-L(5)-CH3(6:12)|VL(7:9)-L(8)-VH(9:7)-H(10:4){3}[MOD:REMCYS][NOTE: Nter 5aa extension Cter 2aa extension]-L(11)-CH3(12:6)

i.e. the extra disulphide is regarded as an extension to the hinge rather than being part of the linker. That's the way the applicants have drawn it (But it would be good to support both!)

[JamesSweetJones]

Hi Andrew,

Using the second expression you gave, I've come up with this, which can be inputted into abYdraw. Let me know what you think

[AndrewCRMartin]

Perfect!

A.

On Tue, 15 Mar 2022 at 13:52, James Sweet-Jones @.***> wrote:

[image: Screenshot 2022-03-15 at 13 51 33] https://user-images.githubusercontent.com/73530578/158392535-2f5307bf-76c6-4e7e-80e1-61088c3022c0.png Hi Andrew,

Using the second expression you gave, I've come up with this, which can be inputted into abYdraw. Let me know what you think

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[AndrewCRMartin]

Re-opened since clicking Get AbML or Tidy doesn't work. But this is non-urgent

As mentioned above:

You could add a H-L (hinge-linker) join type (and a linker-hinge - L-H - at the same time). The H-L would appear as two separate things in the AbML, but a single button on the interface.

[JamesSweetJones]

Think I've cracked it!

James