Each of these two designs attaches a carbonyl-based warhead directly to the amide nitrogen of ADA-UCB-6c2cb422-1. As such, the designs are analogous to PET-UNK-5ecb6237-1 and NIR-WEI-75ed5c39-1. It is intended that the carbonyl oxygen of each warhead should function as a hydrogen bond acceptor in a similar manner to the amide carbonyl oxygen of the quinolone EDJ-MED-6af13d92-3. This would be expected to make the warheads more electrophilic when bound to target. I would anticipate that the first design (N-formyl) has the better chance of adopting the desired conformation. Covalent bond formation with warheads may lead to the designs functioning as substrates (benefits may result from slow dissociation of products).
I am assuming that each design can be synthesized directly from ADA-UCB-6c2cb422-1. The pdb file associated with the submission contains the following: (1) X10959 protein (2) X10959 ligand ADA-UCB-6c2cb422-1 (3) EDJ-MED-6af13d92-3 (4) first design (with formyl warhead) (5) second design (with methoxycarbonyl warhead).