Dataset Information

Synthesis and evaluation of the aldolase antibody-derived chemical-antibodies targeting ?5?1 integrin.

ABSTRACT: Integrin ?5?1 is an important therapeutic target that can be inhibited using an aldolase antibody (Ab)-derived chemical-Ab (chem-Ab) for the treatment of multiple human diseases, including cancers. A fairly optimized anti-integrin ?5?1 chem-Ab 38C2-4e was obtained using an in situ convergent chemical programming (CP) approach, which minimized the time and effort needed to develop a chem-Ab. Multiple Ab-programming agents (PAs) 4a-e could be prepared rapidly using the Cu-catalyzed alkyne-azide coupling (Cu-AAC) reaction of an ?5?1 inhibitor 2 with multiple linkers 3a-e, either before or after conjugating the linkers into Ab 38C2 binding sites. In these two-steps processes, the products after step 1 can be used in the next step without performing an extensive purification or analysis of the Ab-PAs or Ab-linker conjugates affording chem-Abs 38C2-(4a-e). Flow cytometry assay was used to determine the binding of the chem-Abs to U87 human glioblastoma cells expressing ?5?1 integrin and identify 38C2-3e as the strongest binder. Further studies revealed that 38C2-3e strongly inhibited proliferation of U87 cells and tube formation of HUVEC in the matrigel assay, as well as tumor growth and metastasis of 4T1 cells in vivo.

SUBMITTER: Goswami RK

PROVIDER: S-EPMC3596504 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthesis and evaluation of the aldolase antibody-derived chemical-antibodies targeting α5β1 integrin.

Goswami Rajib K RK Liu Yuan Y Liu Cheng C Lerner Richard A RA Sinha Subhash C SC

Molecular pharmaceutics 20121114 2

Integrin α5β1 is an important therapeutic target that can be inhibited using an aldolase antibody (Ab)-derived chemical-Ab (chem-Ab) for the treatment of multiple human diseases, including cancers. A fairly optimized anti-integrin α5β1 chem-Ab 38C2-4e was obtained using an in situ convergent chemical programming (CP) approach, which minimized the time and effort needed to develop a chem-Ab. Multiple Ab-programming agents (PAs) 4a-e could be prepared rapidly using the Cu-catalyzed alkyne-azide co ...[more]

PMID: 23102054

Similar Datasets

Project description:Sperm selection for assisted reproduction techniques is generally based on basic parameters, while key aspects of sperm competence and its journey from the deposition site to the fertilization site are overlooked. Consequently, identifying molecular markers in spermatozoa that can efficiently predict the fertility of a semen sample could be of great interest, particularly in cases of idiopathic male infertility. When spermatozoa reach the female reproductive tract, it provides to them the cellular and molecular microenvironment needed to acquire fertilizing ability. In this sense, considering the role that integrin α5β1 of spermatozoa plays in reproduction-related events, we investigated the correlation between the subcellular localization of sperm integrin α5β1 and early embryo development outcome after in vitro fertilization (IVF) procedures in human. Twenty-four semen samples from normozoospermic men and metaphase II (MII) oocytes from healthy women aged under 38 years, from couples who underwent IVF cycles, were used in this work. Sperm α5β1 localization was evaluated by immunofluorescence assay using an antibody against integrin α5 subunit. Integrin α5β1 was mainly localized in the sperm acrosomal region (45.33±7.89%) or the equatorial segment (30.12±7.43%). The early embryo development rate (data obtained from the Fertility Center) correlated positively with the localization of α5β1 in the acrosomal region (number of usable embryos / inseminated oocytes: ρ = 0.75; p<0.01 and number of usable embryos/total number of two pronuclear zygotes: ρ = 0.80; p<0.01). However, this correlation was not significant when the equatorial segment mark was evaluated. In addition, human sperm released from co-culture with bovine oviductal epithelial cells (BOEC) showed a significant enrichment in the acrosomal localization pattern of α5β1 compared to those sperm that were not co-cultured with BOEC (85.20±5.35% vs 35.00±17.09%, respectively, p<0.05). In conclusion, the evaluation of sperm integrin α5β1 immunolocalization could be a useful tool to select sperm with fertilizing ability from human semen samples before IVF procedures.

Dataset Information

Synthesis and evaluation of the aldolase antibody-derived chemical-antibodies targeting ?5?1 integrin.

Publications

Synthesis and evaluation of the aldolase antibody-derived chemical-antibodies targeting α5β1 integrin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets