Relationship with my best friends sister.

I will give another point of view. I have four older brothers and not once I'd consider dating any of their childhood friends and they never asked me out. I never looked at them as potential dating material. It had nothing to do with the fact that my brothers would disapprove (they would probably react the same as your friend, to be honest) or the strange dynamic or conflict that may come from it all. It was the sheer fact I considered my brothers' friends (their childhood ones) to be almost like an extension of my siblings. My brothers friends are kind, respectful, sound and some even good looking but I have or never had any romantic interest or attraction. I would be freaked out myself if any of them asked me out. It would literally feel like I was being asked out by one of my own brothers!

I don't know how close you are to your friend but if you are a childhood friend that came over to the house most of the time and hung around his family home it's almost as if you are his brother and that would feel strange, in my opinion.