Abstract: A method described herein phenotypes a set of mutant strains in a quantitative manner. Specifically, the method characterizes a cellular and subcellular architecture of mutant alleles grown in a variety of conditions using various morphological and molecular markers, combined with automated image acquisition and analysis. Phenotypic features may include the cytoskeleton, organelles, cell morphology, DNA replication state, the relationship of these features to each other, etc. From these features a quantitative “fingerprint” can be generated for each phenotype. This quantitative phenotypic information is made available in a database that links genotype to phenotype. Genes characterized in this manner may be clustered into functional categories, pathways, higher order protein assemblies, and the like.

Abstract: A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 .mu.g FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H.sub.2 N G y V l G n V l G u T r I e S r P o G y A p G y A g T r P e P o L s A g-Gly-Gln-Thr-X-Val-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Fly-Lys-Phe-AS p (wherein X is undefined). The HCBV protein is isolated from the cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g. Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyses the cis-trans isomerization of proline-containing peptide bonds.

Abstract: A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 .mu.g FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H.sub.2 N-Gly-Val-Gln-Val-Glu-Thr-Ile-Ser-Pro- Gly-Asp-Gly-Arg-Thr-Phe-Pro-Lys- Ar g-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Gly-Lys-Lys-Phe-As p (wherein X is undefined). The HCB protein is isolated from the cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g., Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyzes the cis-trans isomerization of proline-containing peptide bonds.

Abstract: Novel cyclosporin analogs containing a MeAla or MeAbu residue at the 6-position of the cyclic undecapeptide have been synthesized and found unexpectedly to exhibit antagonistic activity toward cyclosporin A binding to its cytosolic protein receptor, cyclophilin, without being immunosuppressive.