Leu-D-Leu

The purpose of this study is to determine the versatility of the monoclonal antibody anti-Leu-M1 in histiocytosis X diagnosis. This antibody recognizes an unsialylated lacto-N-fucopentaose III (hapen X) carbohydrate moiety that is linked to the cell membrane protein in interdigitating reticulum cells and Langerhans' cells. Previously, the authors have shown that anti-Leu-M1 can be used to stain Reed-Sternberg cells, which are likely related to interdigitating reticulum cells. In this study, the authors tested the usefulness of anti-Leu-M1 in staining formalin-fixed and paraffin-embedded tissue sections from eight patients with histiocytosis X. For staining of histiocytosis X cells, unlike Reed-Sternberg cells in Hodgkin's disease, neuraminidase treatment was required for removal of sialic acid residues from the Leu-M1 antigen. The staining characteristics of anti-Leu-M1 in histiocytosis X cells resembled those of normal Langerhans' cells and lymphocyte and histiocyte variants (L & H cells) in the lymphocyte-predominant type of Hodgkin's disease. The significance of sialylation of Leu-M1 antigen in histiocytosis X cells has yet to be determined in order to correlate the prognosis of the disease. The authors suggest that anti-Leu-M1 used together with neuraminidase treatment is a valuable tool in the diagnosis of histiocytosis X when electron microscopy or frozen sections for OKT6 immunostaining are not available.

Self-assembling peptide materials are promising next-generation materials with applications that include tissue engineering scaffolds, drug delivery, bionanomedicine, and enviro-responsive materials. Despite these advances, synthetic methods to form peptides and peptide-polymer conjugates still largely rely on solid-phase peptide synthesis (SPPS) and N-carboxyanhydride ring-opening polymerization (NCA-ROP), while green methods remain largely undeveloped. This work demonstrates a protease-catalyzed peptide synthesis (PCPS) capable of directly grafting leucine ethyl ester (Leu-OEt) from the C-terminus of a methoxy poly(ethylene glycol)-phenylalanine ethyl ester macroinitiator in a one-pot, aqueous reaction. By using the natural tendency of the growing hydrophobic peptide segment to self-assemble, a large narrowing of the (Leu)x distributions for both mPEG45-b-Phe(Leu)x and oligo(Leu)x coproducts, relative to oligo(Leu)x synthesized in the absence of a macroinitiator (mPEG45-Phe-OEt), was achieved. A mechanism is described where in situ β-sheet coassembly of mPEG45-b-Phe(Leu)x and oligo(Leu)x coproducts during polymerization prevents peptide hydrolysis, providing a means to control the degree of polymerization (DP) and dispersity of diblock (Leu)x segments (matrix-assisted laser desorption time-of-flight (MALDI-TOF) x = 5.1, dispersity ≤ 1.02). The use of self-assembly to control the uniformity of peptides synthesized by PCPS paves the way for precise peptide block copolymer architectures with various polymer backbones and amino acid compositions synthesized by a green process.

To investigate the sequence requirements for measles virus (MV)-induced receptor down regulation, we transfected the human CD46 gene into simian cells persistently infected by the Biken strain of MV. Surface expression of CD46 is drastically reduced in these cells. Deletion analysis has shown that the juxtamembrane region of the CD46 cytoplasmic domain is essential for down regulation. Deleting a Tyr-Arg-Tyr-Leu sequence in this region or changing these residues to Ala prevents CD46 down regulation from the infected cell surface. Alanine-scanning mutagenesis has identified two amino acid residues, Tyr and Leu, forming a Tyr-X-X-Leu motif critical for CD46 down regulation. Mutations that prevent CD46 down regulation enhance syncytium formation. These results indicate that CD46 down regulation limits the cytopathic effects in a persistent MV infection and that CD46 down regulation requires a cytoplasmic Tyr-X-X-Leu sequence which resembles known motifs for membrane protein trafficking and receptor signalling.