Several analogs of somatostatin with conformational constraints in their peptide backbones have been modeled to determine energetically feasible conformations. Comparison of low-energy backbone structures of these peptides suggested unique conformations of the central Phe/Alai-D-Trpi+1-Lysi+2-Thri+3 fragment characteristic for specific interactions of somatostatin with each of the five distinct subtypes of somatostatin receptors (SSTRs). The conformations obtained were in good agreement with experimental data obtained earlier by NMR measurements and/or X-ray crystallography. The results help rationalize experimental observations on the specificity of binding of various somatostatin analogs with different subtypes of the SSTRs. They also serve as templates for the design of conformationally constrained non-peptide scaffolds that effectively and selectively interact with different subtypes of SSTRs. Such scaffolds can be convenient carriers of radiolabels and near-infrared labels in specific agents for imaging tumors expressing different SSTR subtypes.