Title

Modification of Lovastatin to Expand Selectivity to MMP-9 for the Treatment of Fragile X Syndrome

Author(s)

Mia KimFollow

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Physiology and Health

Presentation Type

Mentored

Abstract

Fragile X syndrome (FXS) is an X-linked dominant disorder caused by the amplification of the CGG triple at the 5’ end of the fragile X mental retardation 1 gene (FMR-1). The most common non-physical symptoms of FXS include developmental delays and hyperactive behaviors, both of which can be associated with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Over the past several decades, there has been growing interest in the development of drugs to treat FXS. However, due to its primary cause being an error in DNA replication, it is difficult to treat. As such, several pharmaceuticals have been developed to target potential proteins that are downstream of the FMR-1 gene and assist with the production of the fragile X mental retardation protein (FMRP). Two of these such proteins are ERK and MMP-9. In this work, lovastatin, a drug that inhibits ERK activity, was modified to increase its binding affinity to ERK and MMP-9 in an attempt to further relieve effects of the syndrome through two biological mechanisms. The addition of polar functional groups to lovastatin showed marked improvement in binding to the two proteins, showing promising results for a new pharmaceutical treatment of FXS.

Location

HSS 203

Start Date

4-2-2022 9:45 AM

Presentation Format

Oral Only

Group Project

No

COinS
 
Apr 2nd, 9:45 AM

Modification of Lovastatin to Expand Selectivity to MMP-9 for the Treatment of Fragile X Syndrome

HSS 203

Fragile X syndrome (FXS) is an X-linked dominant disorder caused by the amplification of the CGG triple at the 5’ end of the fragile X mental retardation 1 gene (FMR-1). The most common non-physical symptoms of FXS include developmental delays and hyperactive behaviors, both of which can be associated with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Over the past several decades, there has been growing interest in the development of drugs to treat FXS. However, due to its primary cause being an error in DNA replication, it is difficult to treat. As such, several pharmaceuticals have been developed to target potential proteins that are downstream of the FMR-1 gene and assist with the production of the fragile X mental retardation protein (FMRP). Two of these such proteins are ERK and MMP-9. In this work, lovastatin, a drug that inhibits ERK activity, was modified to increase its binding affinity to ERK and MMP-9 in an attempt to further relieve effects of the syndrome through two biological mechanisms. The addition of polar functional groups to lovastatin showed marked improvement in binding to the two proteins, showing promising results for a new pharmaceutical treatment of FXS.