X-ray crystal structure of cyclic-(N-Me-VRGDf) bound to αvβ3 integrin revealing the exposed D-Phe and N-Me-Val as potential attachment points for conjugate synthesis. On this basis, doxorubicin-formaldehyde conjugate was tethered to the para position of the D-Phe via a salicylamide time-release mechanism. Attachment of the drug to the peptide only lowered the binding IC₅₀ by 10-fold (5 nmol/L) even though the molecular weight more than doubled. The doxorubicin-formaldehyde conjugate was a potent inhibitor of MDA-MB-435 breast cancer cell growth in vitro relative to doxorubicin (90 versus 120 nmol/L). The image was created using Pymol modeling software with coordinates obtained from the Protein Data Bank (1L5G) as submitted by Arnaout and co-workers. For details, see Burkhart et al. in this issue.